12-57487850-CAAA-C

Variant summary

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

The ENST00000393797.7(ARHGAP9):c.-204+759_-204+761del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 177,484 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (10 hom., cov: 0)
  • Exomes 𝑓: 0.085 (0 hom.)
• Consequence: ARHGAP9 ENST00000393797.7 intron
• Clinical Significance: Likely 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-CAAA-C is Benign according to our data. Variant chr12-57487850-CAAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1199900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP9	NM_001319850.2	c.-204+759_-204+761del		intron_variant
ARHGAP9	XM_047429329.1	c.10+759_10+761del		intron_variant
ARHGAP9	XM_047429331.1	c.-76+759_-76+761del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP9	ENST00000393797.7	c.-204+759_-204+761del		intron_variant		1
ARHGAP9	ENST00000550288.6	c.-274+759_-274+761del		intron_variant		2
MARS1	ENST00000537638.6	c.-155+47_-155+49del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 790 AN: 68200 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0802

Gnomad SAS AF: 0.00466

Gnomad FIN AF: 0.00171

Gnomad MID AF: 0.0111

Gnomad NFE AF: 0.000584

Gnomad OTH AF: 0.0113

GnomAD4 exome AF: 0.0851 AC: 9305 AN: 109282 Hom.: 0 AF XY: 0.0845 AC XY: 5033 AN XY: 59562

Gnomad4 AFR exome AF: 0.0871

Gnomad4 AMR exome AF: 0.0736

Gnomad4 ASJ exome AF: 0.0830

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.0813

Gnomad4 FIN exome AF: 0.0825

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.0840

GnomAD4 genome AF: 0.0116 AC: 788 AN: 68202 Hom.: 10 Cov.: 0 AF XY: 0.0116 AC XY: 360 AN XY: 31078

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.00394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.00473

Gnomad4 FIN AF: 0.00171

Gnomad4 NFE AF: 0.000584

Gnomad4 OTH AF: 0.0123

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 13, 2020

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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;