13-37637211-C-A

Variant names:

• chr13-37637211-C-A
• rs751793234
• NM_016179.4:c.2626G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016179.4(TRPC4):​c.2626G>T​(p.Ala876Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A876P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TRPC4 NM_016179.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.115799576).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

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.2626G>T	p.Ala876Ser	missense	Exon 11 of 11	NP_057263.1	Q9UBN4-1
	TRPC4	NM_003306.3		c.2641G>T	p.Ala881Ser	missense	Exon 11 of 11	NP_003297.1	Q9UBN4-5
	TRPC4	NM_001135955.3		c.2374G>T	p.Ala792Ser	missense	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.2626G>T	p.Ala876Ser	missense	Exon 11 of 11	ENSP00000369027.4	Q9UBN4-1
	TRPC4	ENST00000625583.2	TSL:1	c.2641G>T	p.Ala881Ser	missense	Exon 10 of 10	ENSP00000486109.1	Q9UBN4-5
	TRPC4	ENST00000358477.6	TSL:1	c.2374G>T	p.Ala792Ser	missense	Exon 12 of 12	ENSP00000351264.2	Q9UBN4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250898 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461634 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111876

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000254 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.12
Sift	Benign	0.20	T
Sift4G	Benign	0.52	T
Polyphen		0.031	B
Vest4		0.27
MVP		0.22
ClinPred		0.21	T
GERP RS		5.8
Varity_R		0.040
gMVP		0.28
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs751793234; hg19: chr13-38211348; COSMIC: COSV59017336;