rs2673931

Variant names:

• chr5-136353748-C-T
• rs2673931
• NM_020389.3:c.780+2860G>A

Variant summary

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

The NM_020389.3(TRPC7):​c.780+2860G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,090 control chromosomes in the GnomAD database, including 33,741 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 0.66 (33741 hom., cov: 33)
• Consequence: TRPC7 NM_020389.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 3 publications found

Genes affected

TRPC7 (HGNC:20754): (transient receptor potential cation channel subfamily C member 7) Predicted to enable inositol 1,4,5 trisphosphate binding activity and store-operated calcium channel activity. Predicted to be involved in metal ion transport; regulation of cytosolic calcium ion concentration; and single fertilization. Predicted to act upstream of or within calcium ion transport. Predicted to be located in plasma membrane. Predicted to be part of cation channel complex. Predicted to be integral component of plasma membrane. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC7	NM_020389.3	c.780+2860G>A		intron_variant	Intron 2 of 11	ENST00000513104.6	NP_065122.1
TRPC7	NM_001376901.1	c.780+2860G>A		intron_variant	Intron 2 of 10		NP_001363830.1
TRPC7	NM_001167577.2	c.780+2860G>A		intron_variant	Intron 2 of 10		NP_001161049.1
TRPC7	NM_001167576.2	c.780+2860G>A		intron_variant	Intron 2 of 9		NP_001161048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC7	ENST00000513104.6	c.780+2860G>A		intron_variant	Intron 2 of 11	5	NM_020389.3	ENSP00000426070.2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100961 AN: 151972 Hom.: 33685 Cov.: 33

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.665 AC: 101079 AN: 152090 Hom.: 33741 Cov.: 33 AF XY: 0.662 AC XY: 49221 AN XY: 74346

African (AFR) AF: 0.698 AC: 28989 AN: 41508

American (AMR) AF: 0.723 AC: 11045 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2597 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3600 AN: 5168

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4820

European-Finnish (FIN) AF: 0.594 AC: 6276 AN: 10560

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43810 AN: 67956

Other (OTH) AF: 0.690 AC: 1461 AN: 2116

Alfa AF: 0.654 Hom.: 4200

Bravo AF: 0.682

Asia WGS AF: 0.630 AC: 2188 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.56
PhyloP100		-0.091
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: rs2673931; hg19: chr5-135689436; COSMIC: COSV61455429;