rs1344142

Positions:

• chr3-56823405-T-C

Variant summary

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

The NM_001128615.2(ARHGEF3):​c.193-49589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,894 control chromosomes in the GnomAD database, including 20,195 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 0.51 (20195 hom., cov: 30)
• Consequence: ARHGEF3 NM_001128615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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]

ARHGEF3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF3	NM_001128615.2	c.193-49589A>G		intron_variant			NP_001122087.1
ARHGEF3	NM_001377407.1	c.193-49589A>G		intron_variant			NP_001364336.1
ARHGEF3	NM_001377408.1	c.133-49589A>G		intron_variant			NP_001364337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF3	ENST00000338458.8	c.193-49589A>G		intron_variant		1		ENSP00000341071.4
ARHGEF3	ENST00000496106.5	c.115-49589A>G		intron_variant		2		ENSP00000420420.1
ARHGEF3	ENST00000473779.5	c.151-49589A>G		intron_variant		3		ENSP00000420402.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77499 AN: 151778 Hom.: 20190 Cov.: 30

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.510 AC: 77541 AN: 151894 Hom.: 20195 Cov.: 30 AF XY: 0.506 AC XY: 37562 AN XY: 74246

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.490

Alfa AF: 0.534 Hom.: 25328

Bravo AF: 0.498

Asia WGS AF: 0.374 AC: 1298 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1344142; hg19: chr3-56857433;