Variant rs16909898 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.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

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:

LOC100507346 (HGNC:):

LOC100507346 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=-0.81).

BP6

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

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PTCH1	NM_000264.5 linkuse as main transcript	c.2250+25T>C	intron_variant		ENST00000331920.11	NP_000255.2
PTCH1	NM_001083603.3 linkuse as main transcript	c.2247+25T>C	intron_variant		ENST00000437951.6	NP_001077072.1
LOC100507346	NR_038982.1 linkuse as main transcript	n.664A>G	non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCH1	ENST00000331920.11 linkuse as main transcript	c.2250+25T>C		intron_variant		5	NM_000264.5	ENSP00000332353	A2	Q13635-1
PTCH1	ENST00000437951.6 linkuse as main transcript	c.2247+25T>C		intron_variant		5	NM_001083603.3	ENSP00000389744		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

GnomAD3 exomes

AF:

0.0841

AC:

21117

AN:

251052

Hom.:

1034

AF XY:

0.0817

AC XY:

11094

AN XY:

135862

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 SAS exome

AF:

0.0387

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

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.0542

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.0815

Gnomad4 SAS exome

AF:

0.0408

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0971

Gnomad4 OTH exome

AF:

0.0844

GnomAD4 genome

AF:

0.102

AC:

15512

AN:

152226

Hom.:

877

Cov.:

AF XY:

0.0978

AC XY:

7281

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.0697

Gnomad4 ASJ

AF:

0.0475

Gnomad4 EAS

AF:

0.0739

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.0974

Gnomad4 NFE

AF:

0.0988

Gnomad4 OTH

AF:

0.0863

Alfa

AF:

0.0930

Hom.:

1395

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

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

- -

Gorlin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.6

DANN

Benign

0.77

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