17-12959042-G-A

Variant names:

• chr17-12959042-G-A
• rs9904572
• NM_014859.6:c.1523+145G>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.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
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014859.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP44	NM_014859.6	MANE Select	c.1523+145G>A		intron	N/A	NP_055674.4
	ARHGAP44	NM_001321166.2		c.1523+145G>A		intron	N/A	NP_001308095.1
	ARHGAP44	NM_001321167.2		c.1523+145G>A		intron	N/A	NP_001308096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP44	ENST00000379672.10	TSL:1 MANE Select	c.1523+145G>A		intron	N/A	ENSP00000368994.5
	ARHGAP44	ENST00000340825.7	TSL:1	c.1523+145G>A		intron	N/A	ENSP00000342566.3
	ARHGAP44	ENST00000262444.13	TSL:1	c.1523+145G>A		intron	N/A	ENSP00000262444.9

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

African (AFR) AF: 0.318 AC: 6649 AN: 20922

American (AMR) AF: 0.400 AC: 13323 AN: 33280

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 7090 AN: 19714

East Asian (EAS) AF: 0.668 AC: 21776 AN: 32604

South Asian (SAS) AF: 0.446 AC: 28029 AN: 62818

European-Finnish (FIN) AF: 0.304 AC: 9761 AN: 32122

Middle Eastern (MID) AF: 0.418 AC: 1772 AN: 4236

European-Non Finnish (NFE) AF: 0.328 AC: 192807 AN: 587500

Other (OTH) AF: 0.372 AC: 14642 AN: 39356

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

African (AFR) AF: 0.313 AC: 12984 AN: 41440

American (AMR) AF: 0.385 AC: 5878 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3587 AN: 5144

South Asian (SAS) AF: 0.463 AC: 2233 AN: 4824

European-Finnish (FIN) AF: 0.305 AC: 3227 AN: 10570

Middle Eastern (MID) AF: 0.417 AC: 121 AN: 290

European-Non Finnish (NFE) AF: 0.334 AC: 22674 AN: 67946

Other (OTH) AF: 0.377 AC: 795 AN: 2110

Alfa AF: 0.348 Hom.: 15937

Bravo AF: 0.355

Asia WGS AF: 0.538 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.50
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: rs9904572; hg19: chr17-12862359; COSMIC: COSV52400625;