chr17-12949075-G-A

Variant names:

• chr17-12949075-G-A
• rs2072255
• NM_014859.6:c.862-65G>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.862-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 1,437,480 control chromosomes in the GnomAD database, including 6,990 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 (947 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6043 hom.)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 12 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 (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.862-65G>A		intron_variant	Intron 10 of 20	ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.862-65G>A		intron_variant	Intron 10 of 20	1	NM_014859.6	ENSP00000368994.5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15949 AN: 152104 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.0919 AC: 118092 AN: 1285258 Hom.: 6043 AF XY: 0.0933 AC XY: 59457 AN XY: 637318

African (AFR) AF: 0.135 AC: 3950 AN: 29278

American (AMR) AF: 0.140 AC: 4947 AN: 35384

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 1194 AN: 24530

East Asian (EAS) AF: 0.181 AC: 6312 AN: 34916

South Asian (SAS) AF: 0.129 AC: 9945 AN: 77086

European-Finnish (FIN) AF: 0.0495 AC: 2110 AN: 42588

Middle Eastern (MID) AF: 0.0771 AC: 425 AN: 5514

European-Non Finnish (NFE) AF: 0.0853 AC: 83754 AN: 981594

Other (OTH) AF: 0.100 AC: 5455 AN: 54368

GnomAD4 genome AF: 0.105 AC: 15969 AN: 152222 Hom.: 947 Cov.: 32 AF XY: 0.106 AC XY: 7858 AN XY: 74418

African (AFR) AF: 0.135 AC: 5626 AN: 41526

American (AMR) AF: 0.123 AC: 1888 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3472

East Asian (EAS) AF: 0.181 AC: 936 AN: 5162

South Asian (SAS) AF: 0.135 AC: 651 AN: 4816

European-Finnish (FIN) AF: 0.0501 AC: 532 AN: 10612

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5862 AN: 68026

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.0943 Hom.: 1189

Bravo AF: 0.112

Asia WGS AF: 0.170 AC: 590 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	0.39
DANN	Benign	0.52
PhyloP100		-1.1
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: rs2072255; hg19: chr17-12852392; COSMIC: COSV52391834; COSMIC: COSV52391834;