Variant 9-95449037-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000264.5(PTCH1):c.3804+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,612,168 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

PTCH1
NM_000264.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00900

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 9-95449037-A-G is Benign according to our data. Variant chr9-95449037-A-G is described in ClinVar as [Benign]. Clinvar id is 255684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-95449037-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00233 (354/152086) while in subpopulation NFE AF= 0.00281 (191/67986). AF 95% confidence interval is 0.00248. There are 2 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 354 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCH1	NM_000264.5 linkuse as main transcript	c.3804+32T>C		intron_variant		ENST00000331920.11	NP_000255.2
PTCH1	NM_001083603.3 linkuse as main transcript	c.3801+32T>C		intron_variant		ENST00000437951.6	NP_001077072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCH1	ENST00000331920.11 linkuse as main transcript	c.3804+32T>C		intron_variant		5	NM_000264.5	ENSP00000332353	A2	Q13635-1
PTCH1	ENST00000437951.6 linkuse as main transcript	c.3801+32T>C		intron_variant		5	NM_001083603.3	ENSP00000389744		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00227

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00281

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00303

AC:

751

AN:

247796

Hom.:

AF XY:

0.00314

AC XY:

422

AN XY:

134544

show subpopulations

Gnomad AFR exome

AF:

0.000445

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00270

Gnomad NFE exome

AF:

0.00358

Gnomad OTH exome

AF:

0.00428

GnomAD4 exome

AF:

0.00277

AC:

4049

AN:

1460082

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

2065

AN XY:

725936

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.0174

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00238

Gnomad4 NFE exome

AF:

0.00276

Gnomad4 OTH exome

AF:

0.00345

GnomAD4 genome

AF:

0.00233

AC:

354

AN:

152086

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00227

Gnomad4 NFE

AF:

0.00281

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00229

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Gorlin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over