13-37636909-T-C

Variant names:

• chr13-37636909-T-C
• rs731860
• NM_016179.4:c.2928A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016179.4(TRPC4):​c.2928A>G​(p.Arg976Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,609,486 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (193 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (199 hom.)
• Consequence: TRPC4 NM_016179.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0910
• Publications: 1 publications found

Genes affected

TRPC4 (HGNC:12336): (transient receptor potential cation channel subfamily C member 4) This gene encodes a member of the canonical subfamily of transient receptor potential cation channels. The encoded protein forms a non-selective calcium-permeable cation channel that is activated by Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ENSG00000297050 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 13-37636909-T-C is Benign according to our data. Variant chr13-37636909-T-C is described in ClinVar as Benign. ClinVar VariationId is 778695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.091 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016179.4. 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
	TRPC4	NM_016179.4	MANE Select	c.2928A>G	p.Arg976Arg	synonymous	Exon 11 of 11	NP_057263.1	Q9UBN4-1
	TRPC4	NM_003306.3		c.2943A>G	p.Arg981Arg	synonymous	Exon 11 of 11	NP_003297.1	Q9UBN4-5
	TRPC4	NM_001135955.3		c.2676A>G	p.Arg892Arg	synonymous	Exon 12 of 12	NP_001129427.1	Q9UBN4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4	ENST00000379705.8	TSL:1 MANE Select	c.2928A>G	p.Arg976Arg	synonymous	Exon 11 of 11	ENSP00000369027.4	Q9UBN4-1
	TRPC4	ENST00000625583.2	TSL:1	c.2943A>G	p.Arg981Arg	synonymous	Exon 10 of 10	ENSP00000486109.1	Q9UBN4-5
	TRPC4	ENST00000358477.6	TSL:1	c.2676A>G	p.Arg892Arg	synonymous	Exon 12 of 12	ENSP00000351264.2	Q9UBN4-2

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4263 AN: 152086 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00766 AC: 1901 AN: 248032 AF XY: 0.00544

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00560

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000348

Gnomad OTH exome AF: 0.00531

GnomAD4 exome AF: 0.00290 AC: 4232 AN: 1457282 Hom.: 199 Cov.: 31 AF XY: 0.00250 AC XY: 1814 AN XY: 724566

African (AFR) AF: 0.0980 AC: 3263 AN: 33286

American (AMR) AF: 0.00705 AC: 313 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000233 AC: 20 AN: 85764

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53192

Middle Eastern (MID) AF: 0.00926 AC: 53 AN: 5726

European-Non Finnish (NFE) AF: 0.000123 AC: 136 AN: 1109362

Other (OTH) AF: 0.00741 AC: 446 AN: 60174

GnomAD4 genome AF: 0.0281 AC: 4271 AN: 152204 Hom.: 193 Cov.: 32 AF XY: 0.0277 AC XY: 2063 AN XY: 74428

African (AFR) AF: 0.0965 AC: 4004 AN: 41508

American (AMR) AF: 0.0114 AC: 174 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68002

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0109 Hom.: 101

Bravo AF: 0.0330

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.69
DANN	Benign	0.52
PhyloP100		-0.091
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: rs731860; hg19: chr13-38211046;