ENST00000428041.4:c.721G>C

Variant names:

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

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>C​(p.Val241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,136 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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=0.0794628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP11B	NM_001039841.3	c.721G>C	p.Val241Leu	missense_variant	Exon 6 of 7		NP_001034930.1
ARHGAP11B	NR_148423.2	n.1414G>C		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>C	p.Val241Leu	missense_variant	Exon 6 of 15			ENSP00000510601.1
ARHGAP11B	ENST00000697964.2	c.721G>C	p.Val241Leu	missense_variant	Exon 6 of 7			ENSP00000513489.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461136 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726912

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111404

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.21
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.28	T;.
M_CAP	Benign	0.00082	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.75	N;.
PhyloP100		2.2
PROVEAN	Benign	-0.38	N;.
REVEL	Benign	0.067
Sift	Benign	0.81	T;.
Polyphen		0.0040	B;.
Vest4		0.15
MutPred		0.55		Loss of catalytic residue at V241 (P = 0.0997);Loss of catalytic residue at V241 (P = 0.0997);
MVP		0.055
MPC		0.45
ClinPred		0.037	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.076
gMVP		0.17
Mutation Taster		=97/3	polymorphism

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;