rs511752

Positions:

• chr12-57483373-T-C

Variant summary

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

The ENST00000393797.7(ARHGAP9):​c.-135+522A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,056 control chromosomes in the GnomAD database, including 2,672 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 0.18 (2672 hom., cov: 31)
• Consequence: ARHGAP9 ENST00000393797.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP9	NM_001319850.2	c.-135+522A>G		intron_variant			NP_001306779.2
ARHGAP9	XM_011538656.3	c.-135+522A>G		intron_variant			XP_011536958.1
ARHGAP9	XM_011538659.3	c.-135+522A>G		intron_variant			XP_011536961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP9	ENST00000393797.7	c.-135+522A>G		intron_variant		1		ENSP00000377386
ARHGAP9	ENST00000550288.6	c.-135+522A>G		intron_variant		2		ENSP00000473445
MARS1	ENST00000549133.1	n.406-4013T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27135 AN: 151934 Hom.: 2659 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.179 AC: 27181 AN: 152056 Hom.: 2672 Cov.: 31 AF XY: 0.184 AC XY: 13712 AN XY: 74338

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.166

Alfa AF: 0.164 Hom.: 267

Bravo AF: 0.178

Asia WGS AF: 0.180 AC: 630 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	1.8
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs511752; hg19: chr12-57877156;