3-56799951-T-C

Variant names:

• chr3-56799951-T-C
• rs1392702
• NM_019555.3:c.96+1752A>G

Variant summary

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

The NM_019555.3(ARHGEF3):​c.96+1752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,076 control chromosomes in the GnomAD database, including 17,089 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 0.43 (17089 hom., cov: 32)
• Consequence: ARHGEF3 NM_019555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF3	NM_019555.3	c.96+1752A>G		intron_variant	Intron 1 of 9	ENST00000296315.8	NP_062455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF3	ENST00000296315.8	c.96+1752A>G		intron_variant	Intron 1 of 9	1	NM_019555.3	ENSP00000296315.3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65791 AN: 151958 Hom.: 17084 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.433 AC: 65789 AN: 152076 Hom.: 17089 Cov.: 32 AF XY: 0.438 AC XY: 32562 AN XY: 74348

African (AFR) AF: 0.158 AC: 6540 AN: 41512

American (AMR) AF: 0.469 AC: 7172 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5180

South Asian (SAS) AF: 0.475 AC: 2287 AN: 4814

European-Finnish (FIN) AF: 0.711 AC: 7509 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38336 AN: 67938

Other (OTH) AF: 0.408 AC: 860 AN: 2110

Alfa AF: 0.511 Hom.: 78144

Bravo AF: 0.400

Asia WGS AF: 0.325 AC: 1129 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.71
PhyloP100		-0.55
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: rs1392702; hg19: chr3-56833979;