rs1344142

Variant names:

• chr3-56823405-T-C
• rs1344142
• ENST00000338458.8:c.193-49589A>G

Variant summary

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

The ENST00000338458.8(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 ENST00000338458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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 = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF3	NM_001128615.2	c.193-49589A>G		intron_variant	Intron 4 of 12		NP_001122087.1
ARHGEF3	NM_001377407.1	c.193-49589A>G		intron_variant	Intron 4 of 12		NP_001364336.1
ARHGEF3	NM_001377408.1	c.133-49589A>G		intron_variant	Intron 6 of 14		NP_001364337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF3	ENST00000338458.8	c.193-49589A>G		intron_variant	Intron 4 of 12	1		ENSP00000341071.4
ARHGEF3	ENST00000496106.5	c.115-49589A>G		intron_variant	Intron 2 of 10	2		ENSP00000420420.1
ARHGEF3	ENST00000473779.5	c.151-49589A>G		intron_variant	Intron 3 of 6	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

African (AFR) AF: 0.501 AC: 20762 AN: 41422

American (AMR) AF: 0.398 AC: 6078 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3468

East Asian (EAS) AF: 0.312 AC: 1608 AN: 5146

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4816

European-Finnish (FIN) AF: 0.589 AC: 6213 AN: 10550

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.551 AC: 37431 AN: 67920

Other (OTH) AF: 0.490 AC: 1032 AN: 2106

Alfa AF: 0.530 Hom.: 35402

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
PhyloP100		-1.4
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: rs1344142; hg19: chr3-56857433;