9-95475514-A-G

Position:

• chr9-95475514-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000264.5(PTCH1):​c.1728+520T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,092 control chromosomes in the GnomAD database, including 13,172 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13172 hom., cov: 32)
• Consequence: PTCH1 NM_000264.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCH1	NM_000264.5	c.1728+520T>C		intron_variant		ENST00000331920.11	NP_000255.2
PTCH1	NM_001083603.3	c.1725+520T>C		intron_variant		ENST00000437951.6	NP_001077072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCH1	ENST00000331920.11	c.1728+520T>C		intron_variant		5	NM_000264.5	ENSP00000332353	A2
PTCH1	ENST00000437951.6	c.1725+520T>C		intron_variant		5	NM_001083603.3	ENSP00000389744

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60994 AN: 151974 Hom.: 13119 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61105 AN: 152092 Hom.: 13172 Cov.: 32 AF XY: 0.396 AC XY: 29462 AN XY: 74372

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.373

Alfa AF: 0.398 Hom.: 2222

Bravo AF: 0.400

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2236407; hg19: chr9-98237796;