1-157046632-G-A

Variant names:

• chr1-157046632-G-A
• rs861086
• NM_001377418.1:c.-217C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377418.1(ARHGEF11):​c.-217C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 152,252 control chromosomes in the GnomAD database, including 71,463 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 0.97 (71463 hom., cov: 32)
• Consequence: ARHGEF11 NM_001377418.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

ARHGEF11 (HGNC:14580): (Rho guanine nucleotide exchange factor 11) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. A similar protein in rat interacts with glutamate transporter EAAT4 and modulates its glutamate transport activity. Expression of the rat protein induces the reorganization of the actin cytoskeleton and its overexpression induces the formation of membrane ruffling and filopodia. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF11	NM_001377418.1	c.-217C>T		5_prime_UTR_variant	Exon 1 of 41		NP_001364347.1
ARHGEF11	XM_047435294.1	c.-217C>T		5_prime_UTR_variant	Exon 1 of 40		XP_047291250.1
ARHGEF11	XM_047435301.1	c.-217C>T		5_prime_UTR_variant	Exon 1 of 40		XP_047291257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147203 AN: 152134 Hom.: 71417 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.977

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

GnomAD4 genome AF: 0.968 AC: 147307 AN: 152252 Hom.: 71463 Cov.: 32 AF XY: 0.969 AC XY: 72149 AN XY: 74460

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.990

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.977

Alfa AF: 0.994 Hom.: 63382

Bravo AF: 0.963

Asia WGS AF: 0.991 AC: 3448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs861086; hg19: chr1-157016424;