rs590086

Variant names:

• chr9-130468272-C-T
• rs590086
• NM_054012.4:c.495+1473C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054012.4(ASS1):​c.495+1473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,158 control chromosomes in the GnomAD database, including 48,300 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 0.75 (48300 hom., cov: 32)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• citrullinemia type I

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, G2P
• acute neonatal citrullinemia type I

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• adult-onset citrullinemia type I

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASS1	NM_054012.4	c.495+1473C>T		intron_variant	Intron 6 of 14	ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4	c.495+1473C>T		intron_variant	Intron 7 of 15		NP_000041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10	c.495+1473C>T		intron_variant	Intron 6 of 14	1	NM_054012.4	ENSP00000253004.6

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114147 AN: 152038 Hom.: 48292 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.750 AC: 114183 AN: 152158 Hom.: 48300 Cov.: 32 AF XY: 0.759 AC XY: 56454 AN XY: 74394

African (AFR) AF: 0.319 AC: 13236 AN: 41428

American (AMR) AF: 0.870 AC: 13313 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3141 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5162 AN: 5178

South Asian (SAS) AF: 0.925 AC: 4466 AN: 4826

European-Finnish (FIN) AF: 0.944 AC: 10021 AN: 10612

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62080 AN: 68030

Other (OTH) AF: 0.793 AC: 1675 AN: 2112

Alfa AF: 0.865 Hom.: 159159

Bravo AF: 0.724

Asia WGS AF: 0.902 AC: 3135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.5
DANN	Benign	0.63
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs590086; hg19: chr9-133343659;