rs2673926

Positions:

• chr5-136361936-G-A
• chr5-136361936-G-C
• chr5-136361936-G-T

Variant summary

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

The NM_020389.3(TRPC7):​c.2+3317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,912 control chromosomes in the GnomAD database, including 11,764 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 0.38 (11764 hom., cov: 32)
• Consequence: TRPC7 NM_020389.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC7	NM_020389.3	c.2+3317C>T		intron_variant		ENST00000513104.6	NP_065122.1
TRPC7	NM_001167576.2	c.2+3317C>T		intron_variant			NP_001161048.1
TRPC7	NM_001167577.2	c.2+3317C>T		intron_variant			NP_001161049.1
TRPC7	NM_001376901.1	c.2+3317C>T		intron_variant			NP_001363830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC7	ENST00000513104.6	c.2+3317C>T		intron_variant		5	NM_020389.3	ENSP00000426070	P1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57213 AN: 151794 Hom.: 11728 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.377 AC: 57303 AN: 151912 Hom.: 11764 Cov.: 32 AF XY: 0.371 AC XY: 27559 AN XY: 74262

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.370

Alfa AF: 0.339 Hom.: 2016

Bravo AF: 0.394

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.66

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: rs2673926; hg19: chr5-135697624;