chr5-136295761-A-G

Variant names:

• chr5-136295761-A-G
• rs1392171
• NM_020389.3:c.963+19836T>C

Variant summary

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

The NM_020389.3(TRPC7):​c.963+19836T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,252 control chromosomes in the GnomAD database, including 964 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 0.11 (964 hom., cov: 33)
• Consequence: TRPC7 NM_020389.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC7	NM_020389.3	c.963+19836T>C		intron_variant	Intron 3 of 11	ENST00000513104.6	NP_065122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC7	ENST00000513104.6	c.963+19836T>C		intron_variant	Intron 3 of 11	5	NM_020389.3	ENSP00000426070.2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17057 AN: 152134 Hom.: 965 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0766

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.112 AC: 17055 AN: 152252 Hom.: 964 Cov.: 33 AF XY: 0.110 AC XY: 8225 AN XY: 74442

African (AFR) AF: 0.125 AC: 5189 AN: 41538

American (AMR) AF: 0.0776 AC: 1187 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3470

East Asian (EAS) AF: 0.0766 AC: 397 AN: 5186

South Asian (SAS) AF: 0.106 AC: 511 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1373 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7816 AN: 68018

Other (OTH) AF: 0.108 AC: 228 AN: 2116

Alfa AF: 0.114 Hom.: 1459

Bravo AF: 0.107

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.51
DANN	Benign	0.48
PhyloP100		-0.33
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: rs1392171; hg19: chr5-135631449;