rs16909898

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000264.5(PTCH1):c.2250+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,611,110 control chromosomes in the GnomAD database, including 7,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 877 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6475 hom. )

Consequence

PTCH1
NM_000264.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.00400

Publications

61 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:

LOC100507346 (HGNC:):

LOC100507346 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-95468726-A-G is Benign according to our data. Variant chr9-95468726-A-G is described in ClinVar as Benign. ClinVar VariationId is 255675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCH1	NM_000264.5 link	c.2250+25T>C		intron_variant	Intron 14 of 23	ENST00000331920.11	NP_000255.2	Q13635-1
PTCH1	NM_001083603.3 link	c.2247+25T>C		intron_variant	Intron 14 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.2250+25T>C		intron_variant	Intron 14 of 23	5	NM_000264.5	ENSP00000332353.6		Q13635-1
PTCH1	ENST00000437951.6 link	c.2247+25T>C		intron_variant	Intron 14 of 23	5	NM_001083603.3	ENSP00000389744.2		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15501

AN:

152106

Hom.:

876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0697

Gnomad ASJ

AF:

0.0475

Gnomad EAS

AF:

0.0743

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.0974

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0988

Gnomad OTH

AF:

0.0876

GnomAD2 exomes

AF:

0.0841

AC:

21117

AN:

251052

AF XY:

0.0817

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.0521

Gnomad ASJ exome

AF:

0.0499

Gnomad EAS exome

AF:

0.0768

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0992

Gnomad OTH exome

AF:

0.0858

GnomAD4 exome

AF:

0.0918

AC:

133860

AN:

1458884

Hom.:

6475

Cov.:

AF XY:

0.0903

AC XY:

65585

AN XY:

725938

show subpopulations

African (AFR)

AF:

0.137

AC:

4589

AN:

33408

American (AMR)

AF:

0.0542

AC:

2423

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0516

AC:

1349

AN:

26126

East Asian (EAS)

AF:

0.0815

AC:

3236

AN:

39684

South Asian (SAS)

AF:

0.0408

AC:

3509

AN:

86034

European-Finnish (FIN)

AF:

0.104

AC:

5573

AN:

53384

Middle Eastern (MID)

AF:

0.0623

AC:

359

AN:

5760

European-Non Finnish (NFE)

AF:

0.0971

AC:

107733

AN:

1109444

Other (OTH)

AF:

0.0844

AC:

5089

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

6259

12517

18776

25034

31293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3846

7692

11538

15384

19230

<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:

0.102

AC:

15512

AN:

152226

Hom.:

877

Cov.:

AF XY:

0.0978

AC XY:

7281

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.138

AC:

5717

AN:

41520

American (AMR)

AF:

0.0697

AC:

1066

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0475

AC:

165

AN:

3472

East Asian (EAS)

AF:

0.0739

AC:

383

AN:

5182

South Asian (SAS)

AF:

0.0363

AC:

175

AN:

4820

European-Finnish (FIN)

AF:

0.0974

AC:

1033

AN:

10604

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0988

AC:

6719

AN:

68010

Other (OTH)

AF:

0.0863

AC:

182

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

732

1463

2195

2926

3658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0968

Hom.:

3300

Bravo

AF:

0.102

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gorlin syndrome

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.6

(source)

DANN

Benign

0.77

PhyloP100

0.0040

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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