13-111128713-C-G

Variant names:

• chr13-111128713-C-G
• rs12853515
• NM_001354046.2:c.165+13022C>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.165+13022C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,172 control chromosomes in the GnomAD database, including 1,855 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 0.16 (1855 hom., cov: 33)
• Consequence: ARHGEF7 NM_001354046.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 8 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]

ARHGEF7-IT1 (HGNC:41408): (ARHGEF7 intronic transcript 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF7	NM_001354046.2	c.165+13022C>G		intron_variant	Intron 1 of 21	ENST00000646102.2	NP_001340975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF7	ENST00000646102.2	c.165+13022C>G		intron_variant	Intron 1 of 21		NM_001354046.2	ENSP00000495631.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23922 AN: 152054 Hom.: 1852 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.157 AC: 23926 AN: 152172 Hom.: 1855 Cov.: 33 AF XY: 0.158 AC XY: 11731 AN XY: 74392

African (AFR) AF: 0.151 AC: 6275 AN: 41538

American (AMR) AF: 0.132 AC: 2010 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5176

South Asian (SAS) AF: 0.192 AC: 927 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10588

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11101 AN: 67978

Other (OTH) AF: 0.160 AC: 339 AN: 2116

Alfa AF: 0.155 Hom.: 250

Bravo AF: 0.153

Asia WGS AF: 0.195 AC: 679 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.41
DANN	Benign	0.40
PhyloP100		-1.3
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: rs12853515; hg19: chr13-111781060;