Variant 9-95477838-G-A 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.1348-136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,442,582 control chromosomes in the GnomAD database, including 100,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16099 hom., cov: 33)

Exomes 𝑓: 0.35 ( 84529 hom. )

Consequence

PTCH1
NM_000264.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.363

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:

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=-0.88).

BP6

Variant 9-95477838-G-A is Benign according to our data. Variant chr9-95477838-G-A is described in ClinVar as [Benign]. Clinvar id is 677044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 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.1348-136C>T		intron_variant		ENST00000331920.11	NP_000255.2	Q13635-1
PTCH1	NM_001083603.3 linkuse as main transcript	c.1345-136C>T		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.1348-136C>T		intron_variant		5	NM_000264.5	ENSP00000332353.6		Q13635-1
PTCH1	ENST00000437951.6 linkuse as main transcript	c.1345-136C>T		intron_variant		5	NM_001083603.3	ENSP00000389744.2		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65958

AN:

151962

Hom.:

16042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.389

GnomAD4 exome

AF:

0.355

AC:

457572

AN:

1290502

Hom.:

84529

AF XY:

0.352

AC XY:

225598

AN XY:

640532

show subpopulations

Gnomad4 AFR exome

AF:

0.668

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.434

AC:

66078

AN:

152080

Hom.:

16099

Cov.:

AF XY:

0.428

AC XY:

31785

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.660

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.343

Gnomad4 SAS

AF:

0.253

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.394

Alfa

AF:

0.373

Hom.:

18936

Bravo

AF:

0.436

Asia WGS

AF:

0.326

AC:

1134

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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

-0.88

CADD

Benign

2.1

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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