NM_014859.6:c.198+4722A>G

Variant names:

• chr17-12901233-A-G
• rs7209847
• NM_014859.6:c.198+4722A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014859.6(ARHGAP44):​c.198+4722A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,994 control chromosomes in the GnomAD database, including 1,989 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 0.13 (1989 hom., cov: 31)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 5 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 = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.198+4722A>G		intron_variant	Intron 3 of 20	ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.198+4722A>G		intron_variant	Intron 3 of 20	1	NM_014859.6	ENSP00000368994.5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19331 AN: 151876 Hom.: 1986 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.127 AC: 19352 AN: 151994 Hom.: 1989 Cov.: 31 AF XY: 0.130 AC XY: 9645 AN XY: 74294

African (AFR) AF: 0.260 AC: 10763 AN: 41428

American (AMR) AF: 0.0890 AC: 1357 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1738 AN: 5136

South Asian (SAS) AF: 0.229 AC: 1101 AN: 4808

European-Finnish (FIN) AF: 0.0491 AC: 520 AN: 10598

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3211 AN: 67986

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.0744 Hom.: 2992

Bravo AF: 0.134

Asia WGS AF: 0.266 AC: 922 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	6.7
DANN	Benign	0.86
PhyloP100		1.6
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: rs7209847; hg19: chr17-12804550;