3-56775600-A-T

Variant names:

• chr3-56775600-A-T
• rs7646054
• ENST00000413728.6:c.-487T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001128616.2(ARHGEF3):​c.-487T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF3 NM_001128616.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128616.2. 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.97-1784T>A		intron	N/A	NP_062455.1
	ARHGEF3	NM_001128616.2		c.-487T>A		5_prime_UTR	Exon 1 of 10	NP_001122088.1
	ARHGEF3	NM_001377413.1		c.-487T>A		5_prime_UTR	Exon 1 of 10	NP_001364342.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF3	ENST00000413728.6	TSL:1	c.-487T>A		5_prime_UTR	Exon 1 of 10	ENSP00000410922.2
	ARHGEF3	ENST00000296315.8	TSL:1 MANE Select	c.97-1784T>A		intron	N/A	ENSP00000296315.3
	ARHGEF3	ENST00000338458.8	TSL:1	c.193-1784T>A		intron	N/A	ENSP00000341071.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 833332 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 384842

African (AFR) AF: 0.00 AC: 0 AN: 15788

American (AMR) AF: 0.00 AC: 0 AN: 996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5154

East Asian (EAS) AF: 0.00 AC: 0 AN: 3632

South Asian (SAS) AF: 0.00 AC: 0 AN: 16482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 762062

Other (OTH) AF: 0.00 AC: 0 AN: 27310

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		0.18
PromoterAI		-0.033	Neutral

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: rs7646054; hg19: chr3-56809628;