chr17-12949142-A-G

Variant names:

• chr17-12949142-A-G
• rs2072254
• NM_014859.6:c.864A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014859.6(ARHGAP44):​c.864A>G​(p.Gly288Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,564,524 control chromosomes in the GnomAD database, including 7,279 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (593 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6686 hom.)
• Consequence: ARHGAP44 NM_014859.6 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 15 publications found

Genes affected

ARHGAP44 (HGNC:29096): (Rho GTPase activating protein 44) Enables phospholipid binding activity. Predicted to be involved in several processes, including modification of dendritic spine; negative regulation of Rac protein signal transduction; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014859.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP44	NM_014859.6	MANE Select	c.864A>G	p.Gly288Gly	splice_region synonymous	Exon 11 of 21	NP_055674.4
	ARHGAP44	NM_001321166.2		c.864A>G	p.Gly288Gly	splice_region synonymous	Exon 11 of 20	NP_001308095.1
	ARHGAP44	NM_001321167.2		c.864A>G	p.Gly288Gly	splice_region synonymous	Exon 11 of 22	NP_001308096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP44	ENST00000379672.10	TSL:1 MANE Select	c.864A>G	p.Gly288Gly	splice_region synonymous	Exon 11 of 21	ENSP00000368994.5
	ARHGAP44	ENST00000340825.7	TSL:1	c.864A>G	p.Gly288Gly	splice_region synonymous	Exon 11 of 20	ENSP00000342566.3
	ARHGAP44	ENST00000262444.13	TSL:1	c.864A>G	p.Gly288Gly	splice_region synonymous	Exon 11 of 22	ENSP00000262444.9

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 12384 AN: 151752 Hom.: 595 Cov.: 32

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0761

GnomAD2 exomes AF: 0.0969 AC: 17092 AN: 176474 AF XY: 0.0977

Gnomad AFR exome AF: 0.0408

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.0521

Gnomad EAS exome AF: 0.182

Gnomad FIN exome AF: 0.0463

Gnomad NFE exome AF: 0.0824

Gnomad OTH exome AF: 0.0934

GnomAD4 exome AF: 0.0925 AC: 130653 AN: 1412654 Hom.: 6686 Cov.: 32 AF XY: 0.0939 AC XY: 65546 AN XY: 698050

African (AFR) AF: 0.0435 AC: 1401 AN: 32170

American (AMR) AF: 0.135 AC: 5032 AN: 37216

Ashkenazi Jewish (ASJ) AF: 0.0509 AC: 1287 AN: 25290

East Asian (EAS) AF: 0.184 AC: 6736 AN: 36648

South Asian (SAS) AF: 0.131 AC: 10504 AN: 79922

European-Finnish (FIN) AF: 0.0507 AC: 2538 AN: 50100

Middle Eastern (MID) AF: 0.0731 AC: 418 AN: 5720

European-Non Finnish (NFE) AF: 0.0892 AC: 96929 AN: 1086868

Other (OTH) AF: 0.0989 AC: 5808 AN: 58720

GnomAD4 genome AF: 0.0816 AC: 12390 AN: 151870 Hom.: 593 Cov.: 32 AF XY: 0.0818 AC XY: 6068 AN XY: 74224

African (AFR) AF: 0.0476 AC: 1972 AN: 41394

American (AMR) AF: 0.118 AC: 1805 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.188 AC: 964 AN: 5138

South Asian (SAS) AF: 0.138 AC: 664 AN: 4806

European-Finnish (FIN) AF: 0.0510 AC: 538 AN: 10548

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0884 AC: 6007 AN: 67950

Other (OTH) AF: 0.0786 AC: 165 AN: 2098

Alfa AF: 0.0788 Hom.: 425

Bravo AF: 0.0846

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.3
DANN	Benign	0.79
PhyloP100		-1.1
Mutation Taster		=97/3	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: rs2072254; hg19: chr17-12852459; COSMIC: COSV52391840; COSMIC: COSV52391840;