15-32624202-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_014783.6(ARHGAP11A):c.327A>G(p.Leu109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,612,284 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0022 (4 hom.)
• Consequence: ARHGAP11A NM_014783.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.134

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 15-32624202-A-G is Benign according to our data. Variant chr15-32624202-A-G is described in ClinVar as [Benign]. Clinvar id is 713581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.134 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP11A	NM_014783.6	c.327A>G	p.Leu109=	synonymous_variant	4/12	ENST00000361627.8
ARHGAP11A-SCG5	NM_001368319.1	c.327A>G	p.Leu109=	synonymous_variant	4/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP11A	ENST00000361627.8	c.327A>G	p.Leu109=	synonymous_variant	4/12	1	NM_014783.6	P1
	ENST00000647892.1	n.2132T>C		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.00128 AC: 194 AN: 151270 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000330

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00145

GnomAD3 exomes AF: 0.00113 AC: 278 AN: 246808 Hom.: 0 AF XY: 0.00122 AC XY: 164 AN XY: 133990

Gnomad AFR exome AF: 0.000711

Gnomad AMR exome AF: 0.000234

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.000602

Gnomad SAS exome AF: 0.000298

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00221 AC: 3235 AN: 1460910 Hom.: 4 Cov.: 31 AF XY: 0.00215 AC XY: 1562 AN XY: 726780

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.00273

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.00128 AC: 194 AN: 151374 Hom.: 0 Cov.: 30 AF XY: 0.00108 AC XY: 80 AN XY: 73888

Gnomad4 AFR AF: 0.000580

Gnomad4 AMR AF: 0.000329

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000971

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.0000948

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00155 Hom.: 1

Bravo AF: 0.00124

EpiCase AF: 0.00256

EpiControl AF: 0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	8.6
Dann	Benign	0.65

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: rs145707437; hg19: chr15-32916403;