7-144363761-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005435.4(ARHGEF5):c.1092A>C(p.Ile364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 20)
  • Exomes 𝑓: 0.00030 (14 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF5 NM_005435.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

Genes affected

ARHGEF5 (HGNC:13209): (Rho guanine nucleotide exchange factor 5) Rho GTPases play a fundamental role in numerous cellular processes initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein may be involved in the control of cytoskeletal organization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 7-144363761-A-C is Benign according to our data. Variant chr7-144363761-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.94 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF5	NM_005435.4	c.1092A>C	p.Ile364=	synonymous_variant	2/15	ENST00000056217.10
ARHGEF5	XM_017012623.3	c.1092A>C	p.Ile364=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF5	ENST00000056217.10	c.1092A>C	p.Ile364=	synonymous_variant	2/15	1	NM_005435.4	P1
ARHGEF5	ENST00000498580.5	c.184+908A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 288 AN: 134306 Hom.: 3 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.00744

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000368

Gnomad ASJ AF: 0.000311

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000229

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000505

Gnomad OTH AF: 0.00272

GnomAD3 exomes AF: 0.000912 AC: 65 AN: 71246 Hom.: 6 AF XY: 0.000860 AC XY: 30 AN XY: 34898

Gnomad AFR exome AF: 0.00980

Gnomad AMR exome AF: 0.000277

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000302 AC: 420 AN: 1389166 Hom.: 14 Cov.: 34 AF XY: 0.000293 AC XY: 203 AN XY: 692404

Gnomad4 AFR exome AF: 0.00991

Gnomad4 AMR exome AF: 0.000299

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000471

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000305

Gnomad4 OTH exome AF: 0.000846

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00214 AC: 287 AN: 134406 Hom.: 3 Cov.: 20 AF XY: 0.00203 AC XY: 133 AN XY: 65492

Gnomad4 AFR AF: 0.00742

Gnomad4 AMR AF: 0.000367

Gnomad4 ASJ AF: 0.000311

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000505

Gnomad4 OTH AF: 0.00269

Alfa AF: 0.00179 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

ARHGEF5: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.26
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs776214865; hg19: chr7-144060854;