3-56932218-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ARHGEF3	NM_001128615.2	c.129+26605C>A		intron_variant
ARHGEF3	NM_001377407.1	c.129+26605C>A		intron_variant
ARHGEF3	NM_001377408.1	c.69+26605C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF3	ENST00000338458.8	c.129+26605C>A		intron_variant		1
ARHGEF3	ENST00000468466.1	c.129+26605C>A		intron_variant		4
ARHGEF3	ENST00000468727.5	c.36+26605C>A		intron_variant		3

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

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.731

Alfa AF: 0.745 Hom.: 67715

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2062583; hg19: chr3-56966246;