13-111166485-A-G

Variant names:

• chr13-111166485-A-G
• rs4773330
• NM_001354046.2:c.252+12494A>G

Variant summary

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

The NM_001354046.2(ARHGEF7):​c.252+12494A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,260 control chromosomes in the GnomAD database, including 57,853 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 0.87 (57853 hom., cov: 33)
• Consequence: ARHGEF7 NM_001354046.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.915 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.252+12494A>G		intron	N/A	NP_001340975.1
	ARHGEF7	NM_001113511.2		c.315+7396A>G		intron	N/A	NP_001106983.1
	ARHGEF7	NM_001320852.1		c.252+12494A>G		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.252+12494A>G		intron	N/A	ENSP00000495631.1
	ARHGEF7	ENST00000375741.6	TSL:1	c.315+7396A>G		intron	N/A	ENSP00000364893.2
	ARHGEF7	ENST00000317133.9	TSL:1	c.252+12494A>G		intron	N/A	ENSP00000325994.5

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132530 AN: 152144 Hom.: 57804 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.871 AC: 132640 AN: 152260 Hom.: 57853 Cov.: 33 AF XY: 0.875 AC XY: 65104 AN XY: 74428

African (AFR) AF: 0.813 AC: 33765 AN: 41528

American (AMR) AF: 0.903 AC: 13809 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3240 AN: 3470

East Asian (EAS) AF: 0.876 AC: 4532 AN: 5172

South Asian (SAS) AF: 0.937 AC: 4528 AN: 4830

European-Finnish (FIN) AF: 0.906 AC: 9611 AN: 10610

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60311 AN: 68038

Other (OTH) AF: 0.869 AC: 1834 AN: 2110

Alfa AF: 0.883 Hom.: 174040

Bravo AF: 0.867

Asia WGS AF: 0.893 AC: 3108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.58
PhyloP100		-1.5
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: rs4773330; hg19: chr13-111818832;