rs542278

chr12-57478937-G-A

Variant summary

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

The NM_032496.4(ARHGAP9):c.316+154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,064 control chromosomes in the GnomAD database, including 1,995 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 0.16 (1995 hom., cov: 32)
• Consequence: ARHGAP9 NM_032496.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

Genes affected

ARHGAP9 (HGNC:14130): (Rho GTPase activating protein 9) This gene encodes a member of the Rho-GAP family of GTPase activating proteins. The protein has substantial GAP activity towards several Rho-family GTPases in vitro, converting them to an inactive GDP-bound state. It is implicated in regulating adhesion of hematopoietic cells to the extracellular matrix. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MARS1 (HGNC:6898): (methionyl-tRNA synthetase 1) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase complex and catalyzes the ligation of methionine to tRNA molecules. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP9	NM_032496.4	c.316+154C>T		intron_variant		ENST00000393791.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP9	ENST00000393791.8	c.316+154C>T		intron_variant		1	NM_032496.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23813 AN: 151946 Hom.: 1990 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.157 AC: 23839 AN: 152064 Hom.: 1995 Cov.: 32 AF XY: 0.163 AC XY: 12138 AN XY: 74332

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.140

Alfa AF: 0.139 Hom.: 366

Bravo AF: 0.153

Asia WGS AF: 0.174 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.2
Dann	Benign	0.25

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: rs542278; hg19: chr12-57872720;