rs10521202

Variant names:

• chr17-12911247-G-A
• rs10521202
• NM_014859.6:c.275+2274G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 rank	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.275+2274G>A		intron_variant	Intron 4 of 20	ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.275+2274G>A		intron_variant	Intron 4 of 20	1	NM_014859.6	ENSP00000368994.5

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

African (AFR) AF: 0.219 AC: 9068 AN: 41416

American (AMR) AF: 0.533 AC: 8143 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3472

East Asian (EAS) AF: 0.542 AC: 2796 AN: 5156

South Asian (SAS) AF: 0.453 AC: 2182 AN: 4822

European-Finnish (FIN) AF: 0.561 AC: 5901 AN: 10526

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38859 AN: 67936

Other (OTH) AF: 0.497 AC: 1050 AN: 2112

Alfa AF: 0.539 Hom.: 29688

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
PhyloP100		0.15
Mutation Taster		=100/0	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: rs10521202; hg19: chr17-12814564; COSMIC: COSV52391694;