rs10521204

Positions:

• chr17-12965343-C-A
• chr17-12965343-C-T

Variant summary

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

The NM_014859.6(ARHGAP44):​c.1523+6446C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,182 control chromosomes in the GnomAD database, including 890 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 0.10 (890 hom., cov: 32)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.1523+6446C>A		intron_variant		ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.1523+6446C>A		intron_variant		1	NM_014859.6	ENSP00000368994	P4

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15239 AN: 152064 Hom.: 889 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.100 AC: 15252 AN: 152182 Hom.: 890 Cov.: 32 AF XY: 0.0995 AC XY: 7403 AN XY: 74408

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0375 Hom.: 35

Bravo AF: 0.0985

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.55

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: rs10521204; hg19: chr17-12868660; COSMIC: COSV52400878;