rs16909898

chr9-95468726-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00400

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]

LOC100507346 (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCH1	NM_000264.5	c.2250+25T>C		intron_variant		ENST00000331920.11
PTCH1	NM_001083603.3	c.2247+25T>C		intron_variant		ENST00000437951.6
LOC100507346	NR_038982.1	n.664A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCH1	ENST00000331920.11	c.2250+25T>C		intron_variant		5	NM_000264.5	A2
PTCH1	ENST00000437951.6	c.2247+25T>C		intron_variant		5	NM_001083603.3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15501 AN: 152106 Hom.: 876 Cov.: 32

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

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.: 33 AF XY: 0.0903 AC XY: 65585 AN XY: 725938

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.: 32 AF XY: 0.0978 AC XY: 7281 AN XY: 74440

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:3

Revision: criteria provided, multiple submitters, no conflicts

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

clinical testing

GeneDx

Mar 03, 2015

- -

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

Other links and lift over

dbSNP: rs16909898; hg19: chr9-98231008; COSMIC: COSV59467442; COSMIC: COSV59467442;