rs540140

Positions:

• chr9-130479984-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_054012.4(ASS1):​c.773+184G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 773,552 control chromosomes in the GnomAD database, including 29,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4726 hom., cov: 34)
  • Exomes 𝑓: 0.27 (24307 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.689

Genes affected

ASS1 (HGNC:758): (argininosuccinate synthase 1) The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10 to 14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase. Mutations in the chromosome 9 copy of this gene cause citrullinemia. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2012]

ASS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-130479984-G-T is Benign according to our data. Variant chr9-130479984-G-T is described in ClinVar as [Benign]. Clinvar id is 1261532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASS1	NM_054012.4	c.773+184G>T		intron_variant		ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4	c.773+184G>T		intron_variant			NP_000041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10	c.773+184G>T		intron_variant		1	NM_054012.4	ENSP00000253004.6

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34513 AN: 152106 Hom.: 4726 Cov.: 34

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.273 AC: 169619 AN: 621328 Hom.: 24307 AF XY: 0.275 AC XY: 91723 AN XY: 333742

Gnomad4 AFR exome AF: 0.0743

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.227 AC: 34521 AN: 152224 Hom.: 4726 Cov.: 34 AF XY: 0.225 AC XY: 16767 AN XY: 74422

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.246

Alfa AF: 0.281 Hom.: 8229

Bravo AF: 0.225

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.78

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: rs540140; hg19: chr9-133355371; COSMIC: COSV61689103; COSMIC: COSV61689103;