NM_001354046.2:c.469-3506G>A

Variant names:

• chr13-111214173-G-A
• rs9560010
• NM_001354046.2:c.469-3506G>A

Variant summary

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

The NM_001354046.2(ARHGEF7):​c.469-3506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,130 control chromosomes in the GnomAD database, including 3,031 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 0.17 (3031 hom., cov: 32)
• Consequence: ARHGEF7 NM_001354046.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 6 publications found

Genes affected

ARHGEF7 (HGNC:15607): (Rho guanine nucleotide exchange factor 7) This gene encodes a protein that belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354046.2. 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
	ARHGEF7	NM_001354046.2	MANE Select	c.469-3506G>A		intron	N/A	NP_001340975.1
	ARHGEF7	NM_001113511.2		c.532-3506G>A		intron	N/A	NP_001106983.1
	ARHGEF7	NM_001320852.1		c.469-3506G>A		intron	N/A	NP_001307781.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF7	ENST00000646102.2	MANE Select	c.469-3506G>A		intron	N/A	ENSP00000495631.1
	ARHGEF7	ENST00000375741.6	TSL:1	c.532-3506G>A		intron	N/A	ENSP00000364893.2
	ARHGEF7	ENST00000317133.9	TSL:1	c.469-3506G>A		intron	N/A	ENSP00000325994.5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25306 AN: 152012 Hom.: 3021 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.167 AC: 25344 AN: 152130 Hom.: 3031 Cov.: 32 AF XY: 0.174 AC XY: 12934 AN XY: 74362

African (AFR) AF: 0.104 AC: 4314 AN: 41486

American (AMR) AF: 0.171 AC: 2616 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3468

East Asian (EAS) AF: 0.687 AC: 3546 AN: 5164

South Asian (SAS) AF: 0.254 AC: 1227 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2294 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10533 AN: 67984

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.156 Hom.: 2355

Bravo AF: 0.164

Asia WGS AF: 0.439 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		-0.16
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: rs9560010; hg19: chr13-111866520;