rs2043190

Variant names:

• chr9-130480593-C-T
• rs2043190
• NM_054012.4:c.838+144C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-130480593-C-T
• chr9-130480593-C-A
• chr9-130480593-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_054012.4(ASS1):​c.838+144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 831,026 control chromosomes in the GnomAD database, including 93,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14821 hom., cov: 34)
  • Exomes 𝑓: 0.47 (79093 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.277
• 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, G2P, Myriad Women’s Health
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-130480593-C-T is Benign according to our data. Variant chr9-130480593-C-T is described in ClinVar as Benign. ClinVar VariationId is 1180898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	NM_054012.4	MANE Select	c.838+144C>T		intron	N/A	NP_446464.1	Q5T6L4
	ASS1	NM_000050.4		c.838+144C>T		intron	N/A	NP_000041.2	P00966

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000352480.10	TSL:1 MANE Select	c.838+144C>T		intron	N/A	ENSP00000253004.6	P00966
	ASS1	ENST00000852201.1		c.1033+144C>T		intron	N/A	ENSP00000522260.1
	ASS1	ENST00000852207.1		c.838+144C>T		intron	N/A	ENSP00000522266.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65126 AN: 152116 Hom.: 14812 Cov.: 34

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.471 AC: 319827 AN: 678792 Hom.: 79093 AF XY: 0.473 AC XY: 168218 AN XY: 355846

African (AFR) AF: 0.290 AC: 5204 AN: 17952

American (AMR) AF: 0.511 AC: 17469 AN: 34156

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 9651 AN: 20130

East Asian (EAS) AF: 0.830 AC: 26772 AN: 32250

South Asian (SAS) AF: 0.498 AC: 31659 AN: 63548

European-Finnish (FIN) AF: 0.414 AC: 14026 AN: 33906

Middle Eastern (MID) AF: 0.496 AC: 1328 AN: 2676

European-Non Finnish (NFE) AF: 0.450 AC: 197800 AN: 439942

Other (OTH) AF: 0.465 AC: 15918 AN: 34232

GnomAD4 genome AF: 0.428 AC: 65169 AN: 152234 Hom.: 14821 Cov.: 34 AF XY: 0.431 AC XY: 32096 AN XY: 74428

African (AFR) AF: 0.306 AC: 12717 AN: 41536

American (AMR) AF: 0.470 AC: 7191 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1657 AN: 3472

East Asian (EAS) AF: 0.818 AC: 4239 AN: 5184

South Asian (SAS) AF: 0.488 AC: 2360 AN: 4832

European-Finnish (FIN) AF: 0.420 AC: 4459 AN: 10608

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31144 AN: 67986

Other (OTH) AF: 0.447 AC: 946 AN: 2116

Alfa AF: 0.437 Hom.: 2999

Bravo AF: 0.427

Asia WGS AF: 0.625 AC: 2172 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.58
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2043190; hg19: chr9-133355980; COSMIC: COSV61688823; COSMIC: COSV61688823;