NM_014783.6:c.1345-502C>T

Variant names:

• chr15-32635275-C-T
• rs8037818
• NM_014783.6:c.1345-502C>T

Variant summary

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

The NM_014783.6(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 NM_014783.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 20 publications found

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:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ENSG00000285948 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014783.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP11A	NM_014783.6	MANE Select	c.1345-502C>T		intron	N/A	NP_055598.1	Q6P4F7-1
	ARHGAP11A	NM_001286479.3		c.778-502C>T		intron	N/A	NP_001273408.1	Q6P4F7-3
	ARHGAP11A	NM_001286480.3		c.778-502C>T		intron	N/A	NP_001273409.1	Q6P4F7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP11A	ENST00000361627.8	TSL:1 MANE Select	c.1345-502C>T		intron	N/A	ENSP00000355090.3	Q6P4F7-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.1235+2167C>T		intron	N/A	ENSP00000510771.1	A0A8I5KWH8
	ARHGAP11A	ENST00000567348.5	TSL:1	c.1345-502C>T		intron	N/A	ENSP00000454575.1	Q6P4F7-2

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

African (AFR) AF: 0.828 AC: 34371 AN: 41490

American (AMR) AF: 0.792 AC: 12096 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2593 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3568 AN: 5168

South Asian (SAS) AF: 0.662 AC: 3196 AN: 4826

European-Finnish (FIN) AF: 0.776 AC: 8210 AN: 10580

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52536 AN: 67994

Other (OTH) AF: 0.759 AC: 1602 AN: 2112

Alfa AF: 0.774 Hom.: 184265

Bravo AF: 0.787

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.51
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs8037818; hg19: chr15-32927476;