NM_020389.3:c.2+3317C>T

Variant names:

• chr5-136361936-G-A
• rs2673926
• NM_020389.3:c.2+3317C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC7	NM_020389.3	MANE Select	c.2+3317C>T		intron	N/A	NP_065122.1
	TRPC7	NM_001376901.1		c.2+3317C>T		intron	N/A	NP_001363830.1
	TRPC7	NM_001167577.2		c.2+3317C>T		intron	N/A	NP_001161049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC7	ENST00000513104.6	TSL:5 MANE Select	c.2+3317C>T		intron	N/A	ENSP00000426070.2
	TRPC7	ENST00000502753.4	TSL:5	c.2+3317C>T		intron	N/A	ENSP00000424854.3
	TRPC7	ENST00000378459.7	TSL:5	c.2+3317C>T		intron	N/A	ENSP00000367720.3

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

African (AFR) AF: 0.552 AC: 22852 AN: 41436

American (AMR) AF: 0.313 AC: 4783 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1315 AN: 3462

East Asian (EAS) AF: 0.419 AC: 2156 AN: 5146

South Asian (SAS) AF: 0.206 AC: 991 AN: 4816

European-Finnish (FIN) AF: 0.304 AC: 3206 AN: 10562

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20744 AN: 67902

Other (OTH) AF: 0.370 AC: 781 AN: 2110

Alfa AF: 0.347 Hom.: 3756

Bravo AF: 0.394

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.66
PhyloP100		0.012
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: rs2673926; hg19: chr5-135697624;