chr15-32635275-C-T

Position:

• chr15-32635275-C-T

Variant summary

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

The ENST00000361627.8(ARHGAP11A):​c.1345-502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,118 control chromosomes in the GnomAD database, including 46,765 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 0.78 (46765 hom., cov: 32)
• Consequence: ARHGAP11A ENST00000361627.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

ARHGAP11A (HGNC:15783): (Rho GTPase activating protein 11A) This gene encodes a member of the Rho GTPase activating protein family. In response to DNA damage, the encoded protein interacts with the p53 tumor suppressor protein and stimulates its tetramerization, which results in cell-cycle arrest and apoptosis. A chromosomal deletion that includes this gene is one cause of Prader-Willi syndrome, and an intronic variant of this gene may be associated with sleep duration in children. This gene is highly expressed in colon cancers and in a human basal-like breast cancer cell line. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP11A	NM_014783.6	c.1345-502C>T		intron_variant		ENST00000361627.8	NP_055598.1
ARHGAP11A-SCG5	NM_001368319.1	c.1235+2167C>T		intron_variant			NP_001355248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP11A	ENST00000361627.8	c.1345-502C>T		intron_variant		1	NM_014783.6	ENSP00000355090	P1
	ENST00000647892.1	n.574+1744G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118965 AN: 152000 Hom.: 46724 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.783 AC: 119060 AN: 152118 Hom.: 46765 Cov.: 32 AF XY: 0.780 AC XY: 58032 AN XY: 74378

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.759

Alfa AF: 0.770 Hom.: 78420

Bravo AF: 0.787

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8037818; hg19: chr15-32927476;