9-130455839-A-G

Variant names:

• chr9-130455839-A-G
• rs7860909
• NM_054012.4:c.174+1466A>G

Variant summary

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

The NM_054012.4(ASS1):​c.174+1466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,140 control chromosomes in the GnomAD database, including 8,478 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 0.33 (8478 hom., cov: 34)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	NM_054012.4	MANE Select	c.174+1466A>G		intron	N/A	NP_446464.1
	ASS1	NM_000050.4		c.174+1466A>G		intron	N/A	NP_000041.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000352480.10	TSL:1 MANE Select	c.174+1466A>G		intron	N/A	ENSP00000253004.6
	ASS1	ENST00000372393.7	TSL:5	c.174+1466A>G		intron	N/A	ENSP00000361469.2
	ASS1	ENST00000372394.5	TSL:2	c.174+1466A>G		intron	N/A	ENSP00000361471.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50405 AN: 152022 Hom.: 8474 Cov.: 34

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.331 AC: 50421 AN: 152140 Hom.: 8478 Cov.: 34 AF XY: 0.334 AC XY: 24808 AN XY: 74382

African (AFR) AF: 0.317 AC: 13157 AN: 41510

American (AMR) AF: 0.271 AC: 4140 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1795 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1851 AN: 5152

South Asian (SAS) AF: 0.324 AC: 1566 AN: 4826

European-Finnish (FIN) AF: 0.378 AC: 4004 AN: 10598

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22831 AN: 67980

Other (OTH) AF: 0.324 AC: 685 AN: 2112

Alfa AF: 0.335 Hom.: 33607

Bravo AF: 0.322

Asia WGS AF: 0.294 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		-1.0
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: rs7860909; hg19: chr9-133331226;