3-56932218-G-T

Variant names:

• chr3-56932218-G-T
• rs2062583
• ENST00000338458.8:c.129+26605C>A

Variant summary

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

The ENST00000338458.8(ARHGEF3):​c.129+26605C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,984 control chromosomes in the GnomAD database, including 41,143 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 0.73 (41143 hom., cov: 31)
• Consequence: ARHGEF3 ENST00000338458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 17 publications found

Genes affected

ARHGEF3 (HGNC:683): (Rho guanine nucleotide exchange factor 3) Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF3	NM_001128615.2	c.129+26605C>A		intron_variant	Intron 3 of 12		NP_001122087.1
ARHGEF3	NM_001377407.1	c.129+26605C>A		intron_variant	Intron 3 of 12		NP_001364336.1
ARHGEF3	NM_001377408.1	c.69+26605C>A		intron_variant	Intron 5 of 14		NP_001364337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF3	ENST00000338458.8	c.129+26605C>A		intron_variant	Intron 3 of 12	1		ENSP00000341071.4
ARHGEF3	ENST00000473779.5	c.87+26605C>A		intron_variant	Intron 2 of 6	3		ENSP00000420402.1
ARHGEF3	ENST00000468727.5	c.36+26605C>A		intron_variant	Intron 2 of 7	3		ENSP00000417087.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111074 AN: 151866 Hom.: 41097 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.731 AC: 111171 AN: 151984 Hom.: 41143 Cov.: 31 AF XY: 0.740 AC XY: 54927 AN XY: 74254

African (AFR) AF: 0.644 AC: 26665 AN: 41420

American (AMR) AF: 0.800 AC: 12216 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2297 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4912 AN: 5174

South Asian (SAS) AF: 0.798 AC: 3842 AN: 4814

European-Finnish (FIN) AF: 0.804 AC: 8465 AN: 10532

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50374 AN: 67976

Other (OTH) AF: 0.731 AC: 1543 AN: 2112

Alfa AF: 0.741 Hom.: 153192

Bravo AF: 0.729

Asia WGS AF: 0.857 AC: 2974 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.27
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: rs2062583; hg19: chr3-56966246;