rs7216369

chr17-12956998-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014859.6(ARHGAP44):c.1342+252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 152,250 control chromosomes in the GnomAD database, including 534 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 0.074 (534 hom., cov: 32)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP44	NM_014859.6	c.1342+252C>T		intron_variant		ENST00000379672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.1342+252C>T		intron_variant		1	NM_014859.6	P4

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11178 AN: 152132 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0773

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0736 AC: 11199 AN: 152250 Hom.: 534 Cov.: 32 AF XY: 0.0730 AC XY: 5436 AN XY: 74440

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.0382

Gnomad4 NFE AF: 0.0773

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0684 Hom.: 46

Bravo AF: 0.0723

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.2
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7216369; hg19: chr17-12860315; COSMIC: COSV52400601;