rs2240567

chr17-12916153-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014859.6(ARHGAP44):c.387+142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 681,856 control chromosomes in the GnomAD database, including 7,961 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 0.16 (2934 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5027 hom.)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP44	NM_014859.6	c.387+142C>A		intron_variant		ENST00000379672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.387+142C>A		intron_variant		1	NM_014859.6	P4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24692 AN: 151956 Hom.: 2927 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0833

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0720

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.108 AC: 57283 AN: 529782 Hom.: 5027 AF XY: 0.109 AC XY: 30251 AN XY: 277854

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0800

Gnomad4 NFE exome AF: 0.0690

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.163 AC: 24718 AN: 152074 Hom.: 2934 Cov.: 32 AF XY: 0.163 AC XY: 12131 AN XY: 74350

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0833

Gnomad4 NFE AF: 0.0720

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0907 Hom.: 1508

Bravo AF: 0.174

Asia WGS AF: 0.239 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.20
Dann	Benign	0.45

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: rs2240567; hg19: chr17-12819470; COSMIC: COSV52396492; COSMIC: COSV52396492;