2-130886251-T-C

Variant names:

• chr2-130886251-T-C
• rs13003829
• NM_001367493.1:c.40-27735T>C

Variant summary

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

The NM_001367493.1(ARHGEF4):​c.40-27735T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,914 control chromosomes in the GnomAD database, including 2,136 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 0.15 (2136 hom., cov: 31)
• Consequence: ARHGEF4 NM_001367493.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 4 publications found

Genes affected

ARHGEF4 (HGNC:684): (Rho guanine nucleotide exchange factor 4) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The protein encoded by this gene may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jun 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF4	NM_001367493.1	c.40-27735T>C		intron_variant	Intron 1 of 13	ENST00000409359.7	NP_001354422.1
ARHGEF4	NM_001375900.1	c.40-44701T>C		intron_variant	Intron 1 of 12		NP_001362829.1
ARHGEF4	NM_015320.4	c.-3184-27735T>C		intron_variant	Intron 1 of 14		NP_056135.2
ARHGEF4	NM_001375901.1	c.-142-27735T>C		intron_variant	Intron 1 of 15		NP_001362830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF4	ENST00000409359.7	c.40-27735T>C		intron_variant	Intron 1 of 13	5	NM_001367493.1	ENSP00000386794.3
ARHGEF4	ENST00000526381.2	n.248-27735T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23313 AN: 151796 Hom.: 2129 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.154 AC: 23353 AN: 151914 Hom.: 2136 Cov.: 31 AF XY: 0.156 AC XY: 11608 AN XY: 74266

African (AFR) AF: 0.199 AC: 8213 AN: 41242

American (AMR) AF: 0.228 AC: 3480 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1127 AN: 5182

South Asian (SAS) AF: 0.222 AC: 1071 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1158 AN: 10596

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7363 AN: 67996

Other (OTH) AF: 0.136 AC: 287 AN: 2110

Alfa AF: 0.133 Hom.: 1263

Bravo AF: 0.164

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.87
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13003829; hg19: chr2-131643824;