rs17624218

Positions:

• chr3-142781638-T-C

Variant summary

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

The NM_001251845.2(TRPC1):​c.960+609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,124 control chromosomes in the GnomAD database, including 1,999 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 0.14 (1999 hom., cov: 32)
• Consequence: TRPC1 NM_001251845.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

Genes affected

TRPC1 (HGNC:12333): (transient receptor potential cation channel subfamily C member 1) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC1	NM_001251845.2	c.960+609T>C		intron_variant		ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6	c.960+609T>C		intron_variant		1	NM_001251845.2	ENSP00000419313	P1
TRPC1	ENST00000273482.10	c.858+609T>C		intron_variant		1		ENSP00000273482
TRPC1	ENST00000698238.1	c.1269+609T>C		intron_variant				ENSP00000513620
TRPC1	ENST00000480101.1	n.90+609T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21915 AN: 152008 Hom.: 2001 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.144 AC: 21909 AN: 152124 Hom.: 1999 Cov.: 32 AF XY: 0.145 AC XY: 10770 AN XY: 74378

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.169

Alfa AF: 0.171 Hom.: 327

Bravo AF: 0.133

Asia WGS AF: 0.0760 AC: 262 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.2
DANN	Benign	0.73

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: rs17624218; hg19: chr3-142500480;