5-136238423-C-T

Variant names:

• chr5-136238423-C-T
• rs10463951
• NM_020389.3:c.1845-6874G>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.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
• Publications: 5 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]

TRPC7-AS2 (HGNC:40937): (TRPC7 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020389.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC7	NM_020389.3	MANE Select	c.1845-6874G>A		intron	N/A	NP_065122.1	Q9HCX4-1
	TRPC7	NM_001376901.1		c.1680-6874G>A		intron	N/A	NP_001363830.1	Q70T25
	TRPC7	NM_001167577.2		c.1662-6874G>A		intron	N/A	NP_001161049.1	Q9HCX4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC7	ENST00000513104.6	TSL:5 MANE Select	c.1845-6874G>A		intron	N/A	ENSP00000426070.2	Q9HCX4-1
	TRPC7	ENST00000502753.4	TSL:5	c.1680-6874G>A		intron	N/A	ENSP00000424854.3	Q70T25
	TRPC7	ENST00000378459.7	TSL:5	c.1662-6874G>A		intron	N/A	ENSP00000367720.3	Q9HCX4-3

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

African (AFR) AF: 0.735 AC: 30437 AN: 41424

American (AMR) AF: 0.512 AC: 7815 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2128 AN: 3468

East Asian (EAS) AF: 0.622 AC: 3205 AN: 5152

South Asian (SAS) AF: 0.586 AC: 2816 AN: 4808

European-Finnish (FIN) AF: 0.547 AC: 5776 AN: 10552

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38565 AN: 67942

Other (OTH) AF: 0.616 AC: 1300 AN: 2110

Alfa AF: 0.578 Hom.: 97792

Bravo AF: 0.615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.36
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: rs10463951; hg19: chr5-135574111;