rs720475

Positions:

• chr7-144377836-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005435.4(ARHGEF5):​c.4531+646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,104 control chromosomes in the GnomAD database, including 3,459 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 0.20 (3459 hom., cov: 32)
• Consequence: ARHGEF5 NM_005435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF5	NM_005435.4	c.4531+646G>A		intron_variant		ENST00000056217.10	NP_005426.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF5	ENST00000056217.10	c.4531+646G>A		intron_variant		1	NM_005435.4	ENSP00000056217	P1
ARHGEF5	ENST00000471847.2	c.1297+646G>A		intron_variant		1		ENSP00000418227
ARHGEF5	ENST00000474817.5	c.2130+646G>A		intron_variant		5		ENSP00000418745

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30121 AN: 151986 Hom.: 3460 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.198 AC: 30122 AN: 152104 Hom.: 3459 Cov.: 32 AF XY: 0.196 AC XY: 14562 AN XY: 74356

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.0398

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.232

Alfa AF: 0.247 Hom.: 7013

Bravo AF: 0.188

Asia WGS AF: 0.130 AC: 453 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	0.11
DANN	Benign	0.50

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: rs720475; hg19: chr7-144074929;