rs2546657

Positions:

• chr5-136348047-T-A
• chr5-136348047-T-C
• chr5-136348047-T-G

Variant summary

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

The NM_020389.3(TRPC7):​c.780+8561A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,146 control chromosomes in the GnomAD database, including 33,657 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 (33657 hom., cov: 33)
• Consequence: TRPC7 NM_020389.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34

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=-0.96).
• 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/exons	MANE	Protein	UniProt
TRPC7	NM_020389.3	c.780+8561A>T		intron_variant		ENST00000513104.6	NP_065122.1
TRPC7	NM_001167576.2	c.780+8561A>T		intron_variant			NP_001161048.1
TRPC7	NM_001167577.2	c.780+8561A>T		intron_variant			NP_001161049.1
TRPC7	NM_001376901.1	c.780+8561A>T		intron_variant			NP_001363830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC7	ENST00000513104.6	c.780+8561A>T		intron_variant		5	NM_020389.3	ENSP00000426070	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100850 AN: 152028 Hom.: 33600 Cov.: 33

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.664 AC: 100969 AN: 152146 Hom.: 33657 Cov.: 33 AF XY: 0.661 AC XY: 49178 AN XY: 74376

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.690

Alfa AF: 0.646 Hom.: 3754

Bravo AF: 0.682

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.69

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: rs2546657; hg19: chr5-135683735; COSMIC: COSV61455363;