17-12874085-A-G

Variant names:

• chr17-12874085-A-G
• rs11651483
• NM_014859.6:c.54-20855A>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.54-20855A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,106 control chromosomes in the GnomAD database, including 47,568 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 0.77 (47568 hom., cov: 32)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 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.54-20855A>G		intron	N/A	NP_055674.4
	ARHGAP44	NM_001321166.2		c.54-20855A>G		intron	N/A	NP_001308095.1
	ARHGAP44	NM_001321167.2		c.54-20855A>G		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.54-20855A>G		intron	N/A	ENSP00000368994.5
	ARHGAP44	ENST00000340825.7	TSL:1	c.54-20855A>G		intron	N/A	ENSP00000342566.3
	ARHGAP44	ENST00000262444.13	TSL:1	c.54-20855A>G		intron	N/A	ENSP00000262444.9

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116573 AN: 151988 Hom.: 47560 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.767 AC: 116614 AN: 152106 Hom.: 47568 Cov.: 32 AF XY: 0.768 AC XY: 57152 AN XY: 74378

African (AFR) AF: 0.468 AC: 19387 AN: 41460

American (AMR) AF: 0.839 AC: 12823 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2957 AN: 3472

East Asian (EAS) AF: 0.700 AC: 3618 AN: 5170

South Asian (SAS) AF: 0.721 AC: 3464 AN: 4806

European-Finnish (FIN) AF: 0.917 AC: 9724 AN: 10600

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61849 AN: 67994

Other (OTH) AF: 0.802 AC: 1694 AN: 2112

Alfa AF: 0.868 Hom.: 89026

Bravo AF: 0.748

Asia WGS AF: 0.754 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.51
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: rs11651483; hg19: chr17-12777402; COSMIC: COSV52391522;