chr13-111238209-C-T

Variant names:

• chr13-111238209-C-T
• rs7325443
• NM_001354046.2:c.759+4916C>T

Variant summary

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

The NM_001354046.2(ARHGEF7):​c.759+4916C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,044 control chromosomes in the GnomAD database, including 5,054 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 0.23 (5054 hom., cov: 32)
• Consequence: ARHGEF7 NM_001354046.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF7	NM_001354046.2	c.759+4916C>T		intron_variant	Intron 6 of 21	ENST00000646102.2	NP_001340975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF7	ENST00000646102.2	c.759+4916C>T		intron_variant	Intron 6 of 21		NM_001354046.2	ENSP00000495631.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34654 AN: 151926 Hom.: 5031 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.228 AC: 34721 AN: 152044 Hom.: 5054 Cov.: 32 AF XY: 0.238 AC XY: 17649 AN XY: 74306

African (AFR) AF: 0.184 AC: 7616 AN: 41450

American (AMR) AF: 0.335 AC: 5123 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.777 AC: 4010 AN: 5164

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4816

European-Finnish (FIN) AF: 0.256 AC: 2702 AN: 10560

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12558 AN: 67978

Other (OTH) AF: 0.225 AC: 475 AN: 2108

Alfa AF: 0.205 Hom.: 15746

Bravo AF: 0.239

Asia WGS AF: 0.519 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.50
DANN	Benign	0.55
PhyloP100		-1.6
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: rs7325443; hg19: chr13-111890556;