9-95508364-TGCCGCCGCCGCC-TGCCGCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000264.5(PTCH1):c.-9_-4delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,163,744 control chromosomes in the GnomAD database, including 127 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 11 hom., cov: 22)

Exomes 𝑓: 0.014 ( 116 hom. )

Consequence

PTCH1
NM_000264.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 3.30

Publications

2 publications found

Variant links:

Genes affected

PTCH1 (HGNC:9585): (patched 1) This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. Hedgehog signaling is important in embryonic development and tumorigenesis. The encoded protein is the receptor for the secreted hedgehog ligands, which include sonic hedgehog, indian hedgehog and desert hedgehog. Following binding by one of the hedgehog ligands, the encoded protein is trafficked away from the primary cilium, relieving inhibition of the G-protein-coupled receptor smoothened, which results in activation of downstream signaling. Mutations of this gene have been associated with basal cell nevus syndrome and holoprosencephaly. [provided by RefSeq, Aug 2017]

PTCH1 Gene-Disease associations (from GenCC):

basal cell nevus syndrome 1
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
holoprosencephaly 7
Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
nevoid basal cell carcinoma syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
holoprosencephaly
Inheritance: AD Classification: LIMITED Submitted by: Illumina

PTCH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 9-95508364-TGCCGCC-T is Benign according to our data. Variant chr9-95508364-TGCCGCC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00908 (1343/147830) while in subpopulation SAS AF = 0.0139 (66/4750). AF 95% confidence interval is 0.0129. There are 11 homozygotes in GnomAd4. There are 574 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High AC in GnomAd4 at 1343 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCH1	NM_000264.5 link	c.-9_-4delGGCGGC		5_prime_UTR_variant	Exon 1 of 24	ENST00000331920.11	NP_000255.2	Q13635-1
PTCH1	NM_001083603.3 link	c.199-1771_199-1766delGGCGGC		intron_variant	Intron 1 of 23	ENST00000437951.6	NP_001077072.1	Q13635-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCH1	ENST00000331920.11 link	c.-9_-4delGGCGGC		5_prime_UTR_variant	Exon 1 of 24	5	NM_000264.5	ENSP00000332353.6		Q13635-1
PTCH1	ENST00000437951.6 link	c.199-1771_199-1766delGGCGGC		intron_variant	Intron 1 of 23	5	NM_001083603.3	ENSP00000389744.2		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.00910

AC:

1345

AN:

147724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00428

Gnomad AMI

AF:

0.00112

Gnomad AMR

AF:

0.00784

Gnomad ASJ

AF:

0.0103

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00181

Gnomad MID

AF:

0.0226

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0109

GnomAD2 exomes

AF:

0.0141

AC:

AN:

1492

AF XY:

0.0174

show subpopulations

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0137

AC:

13923

AN:

1015914

Hom.:

116

AF XY:

0.0135

AC XY:

6505

AN XY:

480676

show subpopulations

African (AFR)

AF:

0.00337

AC:

AN:

20162

American (AMR)

AF:

0.00680

AC:

AN:

6618

Ashkenazi Jewish (ASJ)

AF:

0.0105

AC:

116

AN:

11092

East Asian (EAS)

AF:

0.0000957

AC:

AN:

20892

South Asian (SAS)

AF:

0.0119

AC:

227

AN:

19036

European-Finnish (FIN)

AF:

0.00341

AC:

AN:

18172

Middle Eastern (MID)

AF:

0.0230

AC:

AN:

2568

European-Non Finnish (NFE)

AF:

0.0146

AC:

12836

AN:

878538

Other (OTH)

AF:

0.0131

AC:

508

AN:

38836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

702

1403

2105

2806

3508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

598

1196

1794

2392

2990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00908

AC:

1343

AN:

147830

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

574

AN XY:

72028

show subpopulations

African (AFR)

AF:

0.00427

AC:

174

AN:

40742

American (AMR)

AF:

0.00783

AC:

117

AN:

14950

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

AN:

3398

East Asian (EAS)

AF:

0.000202

AC:

AN:

4948

South Asian (SAS)

AF:

0.0139

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00181

AC:

AN:

9392

Middle Eastern (MID)

AF:

0.0241

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0136

AC:

903

AN:

66424

Other (OTH)

AF:

0.0108

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00251

Hom.:

138

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Nov 04, 2021

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2021

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 31, 2015

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:4

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PTCH1: BP4, BS1, BS2 -

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 30, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: c.-9_-4delGGCGGC affects mildly conserved nucleotides, resulting in a deletion of 6 nucleotides in the 5UTR region. This variant was found in 17/5008 control chromosomes of 1000Gs project at a frequency of 0.0034, which greatly exceeds the maximal expected frequency of a pathogenic allele (0.000017). The variant has been reported as Likely Benign by one reputable databases/clinical laboratories without evidence to independently evaluate. Taking together, the variant was classified as Benign. -

Gorlin syndrome

Benign:1

Apr 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Aug 15, 2015

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign);Other data supporting benign classification -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=296/4

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over