12-57487850-CAA-C

Position:

• chr12-57487850-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000393797.7(ARHGAP9):​c.-204+760_-204+761del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 178,422 control chromosomes in the GnomAD database, including 302 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (301 hom., cov: 0)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: ARHGAP9 ENST00000393797.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.443

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 -10 ACMG points.

• BP6: Variant 12-57487850-CAA-C is Benign according to our data. Variant chr12-57487850-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1221110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP9	NM_001319850.2	c.-204+760_-204+761del		intron_variant			NP_001306779.2
ARHGAP9	XM_047429329.1	c.10+760_10+761del		intron_variant			XP_047285285.1
ARHGAP9	XM_047429331.1	c.-76+760_-76+761del		intron_variant			XP_047285287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP9	ENST00000393797.7	c.-204+760_-204+761del		intron_variant		1		ENSP00000377386
ARHGAP9	ENST00000550288.6	c.-274+760_-274+761del		intron_variant		2		ENSP00000473445
MARS1	ENST00000537638.6	c.-155+48_-155+49del		intron_variant, NMD_transcript_variant		2		ENSP00000446168

Frequencies

GnomAD3 genomes AF: 0.154 AC: 10557 AN: 68684 Hom.: 302 Cov.: 0

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0778

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.147 AC: 16161 AN: 109736 Hom.: 1 AF XY: 0.146 AC XY: 8752 AN XY: 59746

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.154 AC: 10556 AN: 68686 Hom.: 301 Cov.: 0 AF XY: 0.156 AC XY: 4871 AN XY: 31272

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.130

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

GeneDx

Oct 27, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10715375; hg19: chr12-57881633;