rs544701

Variant names:

• chr9-130496996-A-G
• rs544701
• NM_054012.4:c.1127+1973A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-130496996-A-G
• chr9-130496996-A-T

Variant summary

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

The ENST00000352480.10(ASS1):​c.1127+1973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,258 control chromosomes in the GnomAD database, including 1,789 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 0.12 (1789 hom., cov: 33)
• Consequence: ASS1 ENST00000352480.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 7 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000352480.10. 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.1127+1973A>G		intron	N/A	NP_446464.1
	ASS1	NM_000050.4		c.1127+1973A>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.1127+1973A>G		intron	N/A	ENSP00000253004.6
	ASS1	ENST00000372393.7	TSL:5	c.1127+1973A>G		intron	N/A	ENSP00000361469.2
	ASS1	ENST00000372394.5	TSL:2	c.1127+1973A>G		intron	N/A	ENSP00000361471.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18506 AN: 152140 Hom.: 1781 Cov.: 33

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.122 AC: 18523 AN: 152258 Hom.: 1789 Cov.: 33 AF XY: 0.125 AC XY: 9311 AN XY: 74448

African (AFR) AF: 0.0270 AC: 1124 AN: 41568

American (AMR) AF: 0.209 AC: 3201 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3466

East Asian (EAS) AF: 0.455 AC: 2355 AN: 5174

South Asian (SAS) AF: 0.169 AC: 814 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10600

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8825 AN: 68008

Other (OTH) AF: 0.129 AC: 272 AN: 2116

Alfa AF: 0.127 Hom.: 2417

Bravo AF: 0.126

Asia WGS AF: 0.329 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.2
DANN	Benign	0.82
PhyloP100		-0.33
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: rs544701; hg19: chr9-133372383;