rs2072254

Positions:

• chr17-12949142-A-G
• chr17-12949142-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ARHGAP44 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.864A>G	p.Gly288Gly	splice_region_variant, synonymous_variant	11/21	ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.864A>G	p.Gly288Gly	splice_region_variant, synonymous_variant	11/21	1	NM_014859.6	ENSP00000368994.5

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

GnomAD3 exomes AF: 0.0969 AC: 17092 AN: 176474 Hom.: 1041 AF XY: 0.0977 AC XY: 9162 AN XY: 93782

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 SAS exome AF: 0.128

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

Gnomad4 AFR exome AF: 0.0435

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.0509

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0507

Gnomad4 NFE exome AF: 0.0892

Gnomad4 OTH exome AF: 0.0989

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

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0531

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.0786

Alfa AF: 0.0761 Hom.: 304

Bravo AF: 0.0846

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.3
DANN	Benign	0.79

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: rs2072254; hg19: chr17-12852459; COSMIC: COSV52391840; COSMIC: COSV52391840;