5-136238423-C-T

Variant summary

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

The NM_020389.3(TRPC7):c.1845-6874G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,928 control chromosomes in the GnomAD database, including 28,740 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 0.61 (28740 hom., cov: 32)
• Consequence: TRPC7 NM_020389.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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]

TRPC7-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC7	NM_020389.3	c.1845-6874G>A		intron_variant		ENST00000513104.6
TRPC7-AS2	NR_133682.1	n.59+11710C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC7	ENST00000513104.6	c.1845-6874G>A		intron_variant		5	NM_020389.3	P1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92560 AN: 151810 Hom.: 28713 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.610 AC: 92630 AN: 151928 Hom.: 28740 Cov.: 32 AF XY: 0.606 AC XY: 45030 AN XY: 74246

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.616

Alfa AF: 0.567 Hom.: 45443

Bravo AF: 0.615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.6
Dann	Benign	0.51

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: rs10463951; hg19: chr5-135574111;