rs13100723

Positions:

• chr3-56764467-C-T

Variant summary

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

The NM_019555.3(ARHGEF3):​c.204+9242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 152,160 control chromosomes in the GnomAD database, including 506 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 0.069 (506 hom., cov: 32)
• Consequence: ARHGEF3 NM_019555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF3	NM_019555.3	c.204+9242G>A		intron_variant		ENST00000296315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF3	ENST00000296315.8	c.204+9242G>A		intron_variant		1	NM_019555.3	P1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10500 AN: 152042 Hom.: 505 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0691 AC: 10510 AN: 152160 Hom.: 506 Cov.: 32 AF XY: 0.0690 AC XY: 5133 AN XY: 74362

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0411

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0824 Hom.: 215

Bravo AF: 0.0684

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.72

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: rs13100723; hg19: chr3-56798495;