rs2046362

Variant names:

• chr15-30644082-A-G
• rs2046362
• ENST00000428041.4:c.*79-557A>G

Variant summary

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

The ENST00000428041.4(ARHGAP11B):​c.*79-557A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,690 control chromosomes in the GnomAD database, including 22,579 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 0.53 (22579 hom., cov: 31)
• Consequence: ARHGAP11B ENST00000428041.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 17 publications found

Genes affected

ARHGAP11B (HGNC:15782): (Rho GTPase activating protein 11B) Predicted to enable GTPase activator activity. Involved in cerebral cortex development and negative regulation of mitochondrial membrane permeability. Acts upstream of with a positive effect on glutamine catabolic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284906 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP11B	NR_148423.2	n.1576-557A>G		intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284906	ENST00000685924.1	c.*79-557A>G		intron_variant	Intron 7 of 14			ENSP00000510601.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80457 AN: 151572 Hom.: 22554 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.531 AC: 80531 AN: 151690 Hom.: 22579 Cov.: 31 AF XY: 0.524 AC XY: 38856 AN XY: 74150

African (AFR) AF: 0.640 AC: 26464 AN: 41360

American (AMR) AF: 0.439 AC: 6688 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1748 AN: 3460

East Asian (EAS) AF: 0.141 AC: 727 AN: 5146

South Asian (SAS) AF: 0.395 AC: 1896 AN: 4804

European-Finnish (FIN) AF: 0.528 AC: 5557 AN: 10528

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35765 AN: 67864

Other (OTH) AF: 0.520 AC: 1092 AN: 2102

Alfa AF: 0.514 Hom.: 21758

Bravo AF: 0.528

Asia WGS AF: 0.320 AC: 1109 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.037
DANN	Benign	0.49
PhyloP100		-1.4

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: rs2046362; hg19: chr15-30936285;