rs666174

Variant names:

• chr9-130486529-G-A
• rs666174
• NM_054012.4:c.839-2804G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-130486529-G-A
• chr9-130486529-G-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.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
• Publications: 4 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=-0.88).
• 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 rank	MANE	Protein	UniProt
ASS1	NM_054012.4	c.839-2804G>A		intron_variant	Intron 11 of 14	ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4	c.839-2804G>A		intron_variant	Intron 12 of 15		NP_000041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10	c.839-2804G>A		intron_variant	Intron 11 of 14	1	NM_054012.4	ENSP00000253004.6

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

African (AFR) AF: 0.238 AC: 9877 AN: 41432

American (AMR) AF: 0.415 AC: 6346 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3042 AN: 5162

South Asian (SAS) AF: 0.439 AC: 2109 AN: 4802

European-Finnish (FIN) AF: 0.301 AC: 3168 AN: 10538

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21701 AN: 67968

Other (OTH) AF: 0.324 AC: 684 AN: 2110

Alfa AF: 0.323 Hom.: 5066

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
PhyloP100		-3.4
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: rs666174; hg19: chr9-133361916;