Variant 9-95444118-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000264.5(PTCH1):c.*2275T>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0884 in 148,238 control chromosomes in the GnomAD database, including 1,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 1596 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 0 hom. )

Consequence

PTCH1
NM_000264.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-95444118-A-T is Benign according to our data. Variant chr9-95444118-A-T is described in ClinVar as [Benign]. Clinvar id is 367628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 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.*2275T>A		3_prime_UTR_variant	24/24	ENST00000331920.11	NP_000255.2
PTCH1	NM_001083603.3 linkuse as main transcript	c.*2275T>A		3_prime_UTR_variant	24/24	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.*2275T>A		3_prime_UTR_variant	24/24	5	NM_000264.5	ENSP00000332353	A2	Q13635-1
PTCH1	ENST00000437951.6 linkuse as main transcript	c.*2275T>A		3_prime_UTR_variant	24/24	5	NM_001083603.3	ENSP00000389744		Q13635-2

Frequencies

GnomAD3 genomes

AF:

0.0885

AC:

13080

AN:

147758

Hom.:

1592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.00554

Gnomad AMR

AF:

0.0513

Gnomad ASJ

AF:

0.0255

Gnomad EAS

AF:

0.0207

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.00585

Gnomad MID

AF:

0.0260

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.0625

GnomAD4 exome

AF:

0.00761

AC:

AN:

394

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

AN XY:

236

show subpopulations

Gnomad4 FIN exome

AF:

0.00769

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0887

AC:

13108

AN:

147844

Hom.:

1596

Cov.:

AF XY:

0.0872

AC XY:

6275

AN XY:

72000

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.0513

Gnomad4 ASJ

AF:

0.0255

Gnomad4 EAS

AF:

0.0209

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.00585

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.0630

Alfa

AF:

0.0747

Hom.:

122

Bravo

AF:

0.101

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Gorlin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Holoprosencephaly 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.9

DANN

Benign

0.82

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