chr11-3633446-C-A

Variant names:

• chr11-3633446-C-A
• rs10834677
• ENST00000526541.2:n.297-846C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000526541.2(TRPC2):​n.297-846C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,118 control chromosomes in the GnomAD database, including 23,903 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 0.51 (23903 hom., cov: 32)
• Consequence: TRPC2 ENST00000526541.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 14 publications found

Genes affected

TRPC2 (HGNC:):

TRPC2 (HGNC:12334): (transient receptor potential cation channel subfamily C member 2 (pseudogene)) Predicted to enable several functions, including calmodulin binding activity; diacylglycerol binding activity; and inositol 1,4,5 trisphosphate binding activity. Predicted to act upstream of or within several processes, including inter-male aggressive behavior; mating behavior; and territorial aggressive behavior. Predicted to be located in several cellular components, including Golgi membrane; dendrite membrane; and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC2	NR_002720.2	n.285-846C>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC2	ENST00000526541.2	n.297-846C>A		intron_variant	Intron 2 of 6	1
TRPC2	ENST00000451043.8	n.1761-846C>A		intron_variant	Intron 7 of 11
TRPC2	ENST00000696867.1	n.361-846C>A		intron_variant	Intron 3 of 7

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77611 AN: 152000 Hom.: 23898 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.510 AC: 77612 AN: 152118 Hom.: 23903 Cov.: 32 AF XY: 0.516 AC XY: 38387 AN XY: 74350

African (AFR) AF: 0.141 AC: 5866 AN: 41506

American (AMR) AF: 0.616 AC: 9413 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3468

East Asian (EAS) AF: 0.653 AC: 3380 AN: 5178

South Asian (SAS) AF: 0.624 AC: 3010 AN: 4824

European-Finnish (FIN) AF: 0.695 AC: 7355 AN: 10578

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44806 AN: 67964

Other (OTH) AF: 0.500 AC: 1056 AN: 2110

Alfa AF: 0.595 Hom.: 55359

Bravo AF: 0.484

Asia WGS AF: 0.609 AC: 2119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.71
PhyloP100		0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10834677; hg19: chr11-3654676;