rs1110866

Variant names:

• chr3-56792296-A-C
• rs1110866
• NM_019555.3:c.96+9407T>G

Variant summary

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

The NM_001128615.2(ARHGEF3):​c.193-18480T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,982 control chromosomes in the GnomAD database, including 8,091 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 0.31 (8091 hom., cov: 31)
• Consequence: ARHGEF3 NM_001128615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128615.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF3	NM_019555.3	MANE Select	c.96+9407T>G		intron	N/A	NP_062455.1
	ARHGEF3	NM_001128615.2		c.193-18480T>G		intron	N/A	NP_001122087.1
	ARHGEF3	NM_001377407.1		c.193-18480T>G		intron	N/A	NP_001364336.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF3	ENST00000296315.8	TSL:1 MANE Select	c.96+9407T>G		intron	N/A	ENSP00000296315.3
	ARHGEF3	ENST00000338458.8	TSL:1	c.193-18480T>G		intron	N/A	ENSP00000341071.4
	ARHGEF3	ENST00000495373.5	TSL:1	c.96+9407T>G		intron	N/A	ENSP00000417986.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47025 AN: 151866 Hom.: 8096 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.309 AC: 47015 AN: 151982 Hom.: 8091 Cov.: 31 AF XY: 0.305 AC XY: 22639 AN XY: 74276

African (AFR) AF: 0.171 AC: 7085 AN: 41456

American (AMR) AF: 0.307 AC: 4695 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1715 AN: 3466

East Asian (EAS) AF: 0.505 AC: 2613 AN: 5176

South Asian (SAS) AF: 0.249 AC: 1198 AN: 4812

European-Finnish (FIN) AF: 0.290 AC: 3058 AN: 10538

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25414 AN: 67940

Other (OTH) AF: 0.391 AC: 826 AN: 2114

Alfa AF: 0.365 Hom.: 42513

Bravo AF: 0.309

Asia WGS AF: 0.335 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		0.40
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: rs1110866; hg19: chr3-56826324;