rs10521202

chr17-12911247-G-A

Variant summary

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

The NM_014859.6(ARHGAP44):c.275+2274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,916 control chromosomes in the GnomAD database, including 18,154 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 0.46 (18154 hom., cov: 31)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP44	NM_014859.6	c.275+2274G>A		intron_variant		ENST00000379672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.275+2274G>A		intron_variant		1	NM_014859.6	P4

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70483 AN: 151800 Hom.: 18145 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.495

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70510 AN: 151916 Hom.: 18154 Cov.: 31 AF XY: 0.464 AC XY: 34455 AN XY: 74238

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.497

Alfa AF: 0.541 Hom.: 25429

Bravo AF: 0.452

Asia WGS AF: 0.490 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.82

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: rs10521202; hg19: chr17-12814564; COSMIC: COSV52391694;