17-12955972-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014859.6(ARHGAP44):c.1242A>G(p.Gln414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,611,652 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (67 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (64 hom.)
• Consequence: ARHGAP44 NM_014859.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0640

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-12955972-A-G is Benign according to our data. Variant chr17-12955972-A-G is described in ClinVar as [Benign]. Clinvar id is 790717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.064 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP44	NM_014859.6	c.1242A>G	p.Gln414=	synonymous_variant	14/21	ENST00000379672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.1242A>G	p.Gln414=	synonymous_variant	14/21	1	NM_014859.6	P4

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2402 AN: 151820 Hom.: 67 Cov.: 31

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00559

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00387 AC: 963 AN: 248790 Hom.: 19 AF XY: 0.00280 AC XY: 378 AN XY: 134972

Gnomad AFR exome AF: 0.0556

Gnomad AMR exome AF: 0.00244

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000798

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00156 AC: 2280 AN: 1459714 Hom.: 64 Cov.: 29 AF XY: 0.00133 AC XY: 965 AN XY: 726280

Gnomad4 AFR exome AF: 0.0566

Gnomad4 AMR exome AF: 0.00293

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.0158 AC: 2407 AN: 151938 Hom.: 67 Cov.: 31 AF XY: 0.0149 AC XY: 1104 AN XY: 74264

Gnomad4 AFR AF: 0.0554

Gnomad4 AMR AF: 0.00558

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00435 Hom.: 16

Bravo AF: 0.0184

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	5.6
Dann	Benign	0.48

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: rs16946898; hg19: chr17-12859289;