rs666174

chr9-130486529-G-Achr9-130486529-G-T

Variant summary

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

The NM_054012.4(ASS1):c.839-2804G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,972 control chromosomes in the GnomAD database, including 8,272 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 0.32 (8272 hom., cov: 32)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.839-2804G>A		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.839-2804G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.839-2804G>A		intron_variant		1	NM_054012.4	P1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48366 AN: 151854 Hom.: 8262 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.319 AC: 48407 AN: 151972 Hom.: 8272 Cov.: 32 AF XY: 0.323 AC XY: 23962 AN XY: 74280

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.324

Alfa AF: 0.318 Hom.: 2375

Bravo AF: 0.322

Asia WGS AF: 0.537 AC: 1865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.35
Dann	Benign	0.80

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: rs666174; hg19: chr9-133361916;