chr2-130931209-C-T

Variant names:

• chr2-130931209-C-T
• rs147260767
• NM_001367493.1:c.3810C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001367493.1(ARHGEF4):​c.3810C>T​(p.His1270His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 1,613,756 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: ARHGEF4 NM_001367493.1 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.105
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-130931209-C-T is Benign according to our data. Variant chr2-130931209-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3051001.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.105 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367493.1. 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
	ARHGEF4	NM_001367493.1	MANE Select	c.3810C>T	p.His1270His	synonymous	Exon 3 of 14	NP_001354422.1	E7EV07
	ARHGEF4	NM_001375900.1		c.297C>T	p.His99His	synonymous	Exon 2 of 13	NP_001362829.1
	ARHGEF4	NM_015320.4		c.252C>T	p.His84His	synonymous	Exon 4 of 15	NP_056135.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF4	ENST00000409359.7	TSL:5 MANE Select	c.3810C>T	p.His1270His	synonymous	Exon 3 of 14	ENSP00000386794.3	E7EV07
	ARHGEF4	ENST00000392953.8	TSL:1	c.324C>T	p.His108His	synonymous	Exon 2 of 12	ENSP00000376680.5	A0A0C4DFY6
	ARHGEF4	ENST00000918336.1		c.3810C>T	p.His1270His	synonymous	Exon 3 of 14	ENSP00000588395.1

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000389 AC: 96 AN: 247076 AF XY: 0.000522

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000554

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000474 AC: 693 AN: 1461436 Hom.: 1 Cov.: 33 AF XY: 0.000534 AC XY: 388 AN XY: 726984

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.000336 AC: 15 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000951 AC: 82 AN: 86202

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53298

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000511 AC: 568 AN: 1111812

Other (OTH) AF: 0.000381 AC: 23 AN: 60378

GnomAD4 genome AF: 0.000355 AC: 54 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31 AN XY: 74486

African (AFR) AF: 0.0000481 AC: 2 AN: 41560

American (AMR) AF: 0.000653 AC: 10 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000518 Hom.: 0

Bravo AF: 0.000340

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ARHGEF4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.1
DANN	Benign	0.85
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism

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: rs147260767; hg19: chr2-131688782;