NM_016179.4:c.1884+769T>G

Variant names:

• chr13-37654319-A-C
• rs7338118
• NM_016179.4:c.1884+769T>G

Variant summary

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

The NM_016179.4(TRPC4):​c.1884+769T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,080 control chromosomes in the GnomAD database, including 5,341 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 0.25 (5341 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 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.1884+769T>G		intron	N/A	NP_057263.1	Q9UBN4-1
	TRPC4	NM_003306.3		c.1884+769T>G		intron	N/A	NP_003297.1	Q9UBN4-5
	TRPC4	NM_001135955.3		c.1884+769T>G		intron	N/A	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.1884+769T>G		intron	N/A	ENSP00000369027.4	Q9UBN4-1
	TRPC4	ENST00000625583.2	TSL:1	c.1884+769T>G		intron	N/A	ENSP00000486109.1	Q9UBN4-5
	TRPC4	ENST00000358477.6	TSL:1	c.1884+769T>G		intron	N/A	ENSP00000351264.2	Q9UBN4-2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37734 AN: 151960 Hom.: 5329 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.248 AC: 37777 AN: 152080 Hom.: 5341 Cov.: 32 AF XY: 0.258 AC XY: 19146 AN XY: 74336

African (AFR) AF: 0.255 AC: 10601 AN: 41492

American (AMR) AF: 0.322 AC: 4920 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3472

East Asian (EAS) AF: 0.677 AC: 3496 AN: 5162

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4824

European-Finnish (FIN) AF: 0.251 AC: 2650 AN: 10570

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13304 AN: 67970

Other (OTH) AF: 0.245 AC: 517 AN: 2112

Alfa AF: 0.228 Hom.: 551

Bravo AF: 0.257

Asia WGS AF: 0.495 AC: 1717 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.8
DANN	Benign	0.83
PhyloP100		0.28
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: rs7338118; hg19: chr13-38228456;