Variant chr9-95459579-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000264.5(PTCH1):c.2887+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,611,910 control chromosomes in the GnomAD database, including 108,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15811 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92990 hom. )

Consequence

PTCH1
NM_000264.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.517

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:

PTCH1 (HGNC:):

PTCH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-95459579-T-C is Benign according to our data. Variant chr9-95459579-T-C is described in ClinVar as [Benign]. Clinvar id is 255678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCH1	NM_000264.5 linkuse as main transcript	c.2887+21A>G		intron_variant		ENST00000331920.11	NP_000255.2	Q13635-1
PTCH1	NM_001083603.3 linkuse as main transcript	c.2884+21A>G		intron_variant		ENST00000437951.6	NP_001077072.1	Q13635-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCH1	ENST00000331920.11 linkuse as main transcript	c.2887+21A>G		intron_variant		5	NM_000264.5	ENSP00000332353.6		Q13635-1
PTCH1	ENST00000437951.6 linkuse as main transcript	c.2884+21A>G		intron_variant		5	NM_001083603.3	ENSP00000389744.2		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65179

AN:

151984

Hom.:

15755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.659

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.375

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.345

AC:

86510

AN:

251098

Hom.:

16510

AF XY:

0.340

AC XY:

46212

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.669

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.352

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.351

AC:

511954

AN:

1459806

Hom.:

92990

Cov.:

AF XY:

0.349

AC XY:

253153

AN XY:

726250

show subpopulations

Gnomad4 AFR exome

AF:

0.670

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.354

GnomAD4 genome

AF:

0.429

AC:

65300

AN:

152104

Hom.:

15811

Cov.:

AF XY:

0.422

AC XY:

31408

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.660

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.413

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.253

Gnomad4 FIN

AF:

0.375

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.388

Alfa

AF:

0.401

Hom.:

2370

Bravo

AF:

0.431

Asia WGS

AF:

0.333

AC:

1158

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Gorlin syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Holoprosencephaly 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

DANN

Benign

0.32

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