chr15-30635547-G-A

Variant names:

• chr15-30635547-G-A
• rs2060274635
• ENST00000428041.4:c.721G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000428041.4(ARHGAP11B):​c.721G>A​(p.Val241Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V241L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
• Consequence: ARHGAP11B ENST00000428041.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15616575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP11B	NM_001039841.3	c.721G>A	p.Val241Met	missense_variant	Exon 6 of 7		NP_001034930.1
ARHGAP11B	NR_148423.2	n.1414G>A		non_coding_transcript_exon_variant	Exon 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284906	ENST00000685924.1	c.721G>A	p.Val241Met	missense_variant	Exon 6 of 15			ENSP00000510601.1
ARHGAP11B	ENST00000697964.2	c.721G>A	p.Val241Met	missense_variant	Exon 6 of 7			ENSP00000513489.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151916 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151916 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74196

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67954

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0064	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.35	T;.
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N;.
PhyloP100		2.2
PROVEAN	Benign	-0.35	N;.
REVEL	Benign	0.056
Sift	Benign	0.040	D;.
Polyphen		0.82	P;.
Vest4		0.23
MutPred		0.45		Loss of catalytic residue at V241 (P = 0.0073);Loss of catalytic residue at V241 (P = 0.0073);
MVP		0.076
MPC		0.69
ClinPred		0.24	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2060274635; hg19: chr15-30927750;