rs2046362

chr15-30644082-A-G

Variant summary

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

The NR_148423.2(ARHGAP11B):n.1576-557A>G variant causes a intron, non coding transcript 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 NR_148423.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ARHGAP11B	NR_148423.2	n.1576-557A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP11B	ENST00000693711.1	c.*170-557A>G		intron_variant				P1

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

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.520

Alfa AF: 0.517 Hom.: 14851

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2046362; hg19: chr15-30936285;