rs17624218

Variant names:

• chr3-142781638-T-C
• rs17624218
• NM_001251845.2:c.960+609T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRPC1	NM_001251845.2	c.960+609T>C		intron_variant	Intron 6 of 12	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6	c.960+609T>C		intron_variant	Intron 6 of 12	1	NM_001251845.2	ENSP00000419313.1
TRPC1	ENST00000273482.10	c.858+609T>C		intron_variant	Intron 5 of 11	1		ENSP00000273482.6
TRPC1	ENST00000698238.1	c.1269+609T>C		intron_variant	Intron 6 of 12			ENSP00000513620.1
TRPC1	ENST00000480101.1	n.90+609T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.0413 AC: 1716 AN: 41534

American (AMR) AF: 0.129 AC: 1977 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.116 AC: 561 AN: 4818

European-Finnish (FIN) AF: 0.219 AC: 2313 AN: 10580

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13878 AN: 67938

Other (OTH) AF: 0.169 AC: 356 AN: 2102

Alfa AF: 0.166 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
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17624218; hg19: chr3-142500480;