NM_014783.6:c.327A>G

Variant names:

• chr15-32624202-A-G
• rs145707437
• NM_014783.6:c.327A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014783.6(ARHGAP11A):​c.327A>G​(p.Leu109Leu) 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
• Publications: 1 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 -11 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 VariationId is 713581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.134 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.327A>G	p.Leu109Leu	synonymous	Exon 4 of 12	NP_055598.1	Q6P4F7-1
	ARHGAP11A	NM_001286479.3		c.-241A>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001273408.1	Q6P4F7-3
	ARHGAP11A	NM_001286480.3		c.-241A>G		5_prime_UTR_premature_start_codon_gain	Exon 5 of 13	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.327A>G	p.Leu109Leu	synonymous	Exon 4 of 12	ENSP00000355090.3	Q6P4F7-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.327A>G	p.Leu109Leu	synonymous	Exon 4 of 14	ENSP00000510771.1	A0A8I5KWH8
	ARHGAP11A	ENST00000567348.5	TSL:1	c.327A>G	p.Leu109Leu	synonymous	Exon 4 of 11	ENSP00000454575.1	Q6P4F7-2

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

GnomAD2 exomes AF: 0.00113 AC: 278 AN: 246808 AF XY: 0.00122

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 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

African (AFR) AF: 0.000568 AC: 19 AN: 33432

American (AMR) AF: 0.000425 AC: 19 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26116

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39686

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86216

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53414

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.00273 AC: 3032 AN: 1111254

Other (OTH) AF: 0.00210 AC: 127 AN: 60346

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

African (AFR) AF: 0.000580 AC: 24 AN: 41394

American (AMR) AF: 0.000329 AC: 5 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.000971 AC: 5 AN: 5150

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.0000948 AC: 1 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00228 AC: 154 AN: 67528

Other (OTH) AF: 0.00143 AC: 3 AN: 2096

Alfa AF: 0.00155 Hom.: 1

Bravo AF: 0.00124

EpiCase AF: 0.00256

EpiControl AF: 0.00184

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.6
DANN	Benign	0.65
PhyloP100		0.13
Mutation Taster		=277/23	polymorphism

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: rs145707437; hg19: chr15-32916403;