rs2546657

Variant names:

• chr5-136348047-T-A
• rs2546657
• NM_020389.3:c.780+8561A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.780+8561A>T		intron	N/A	NP_065122.1
	TRPC7	NM_001376901.1		c.780+8561A>T		intron	N/A	NP_001363830.1
	TRPC7	NM_001167577.2		c.780+8561A>T		intron	N/A	NP_001161049.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC7	ENST00000513104.6	TSL:5 MANE Select	c.780+8561A>T		intron	N/A	ENSP00000426070.2
	TRPC7	ENST00000502753.4	TSL:5	c.780+8561A>T		intron	N/A	ENSP00000424854.3
	TRPC7	ENST00000378459.7	TSL:5	c.780+8561A>T		intron	N/A	ENSP00000367720.3

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

African (AFR) AF: 0.697 AC: 28938 AN: 41534

American (AMR) AF: 0.722 AC: 11038 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2567 AN: 3470

East Asian (EAS) AF: 0.698 AC: 3599 AN: 5154

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4818

European-Finnish (FIN) AF: 0.592 AC: 6271 AN: 10584

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43792 AN: 67974

Other (OTH) AF: 0.690 AC: 1461 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.69
PhyloP100		-3.3
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: rs2546657; hg19: chr5-135683735; COSMIC: COSV61455363;