rs9904572

chr17-12959042-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.1523+145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 984,526 control chromosomes in the GnomAD database, including 65,704 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 0.35 (9784 hom., cov: 32)
  • Exomes 𝑓: 0.36 (55920 hom.)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP44	NM_014859.6	c.1523+145G>A		intron_variant		ENST00000379672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.1523+145G>A		intron_variant		1	NM_014859.6	P4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53017 AN: 151856 Hom.: 9764 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.355 AC: 295849 AN: 832552 Hom.: 55920 Cov.: 11 AF XY: 0.360 AC XY: 153412 AN XY: 425958

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.446

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.349 AC: 53085 AN: 151974 Hom.: 9784 Cov.: 32 AF XY: 0.355 AC XY: 26350 AN XY: 74292

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.377

Alfa AF: 0.349 Hom.: 12715

Bravo AF: 0.355

Asia WGS AF: 0.538 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.8
Dann	Benign	0.50

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: rs9904572; hg19: chr17-12862359; COSMIC: COSV52400625;