rs720475

Variant names:

• chr7-144377836-G-A
• rs720475
• NM_005435.4:c.4531+646G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 74 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005435.4. 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
	ARHGEF5	NM_005435.4	MANE Select	c.4531+646G>A		intron	N/A	NP_005426.2	Q12774-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF5	ENST00000056217.10	TSL:1 MANE Select	c.4531+646G>A		intron	N/A	ENSP00000056217.5	Q12774-1
	ARHGEF5	ENST00000471847.2	TSL:1	c.1297+646G>A		intron	N/A	ENSP00000418227.1	Q12774-2
	ARHGEF5	ENST00000940327.1		c.4531+646G>A		intron	N/A	ENSP00000610386.1

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

African (AFR) AF: 0.111 AC: 4611 AN: 41512

American (AMR) AF: 0.186 AC: 2837 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3468

East Asian (EAS) AF: 0.0398 AC: 206 AN: 5180

South Asian (SAS) AF: 0.189 AC: 911 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2678 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17145 AN: 67958

Other (OTH) AF: 0.232 AC: 490 AN: 2110

Alfa AF: 0.235 Hom.: 15748

Bravo AF: 0.188

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.50
PhyloP100		-0.76
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: rs720475; hg19: chr7-144074929;