rs544701

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054012.4(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 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.1127+1973A>G		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.1127+1973A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.1127+1973A>G		intron_variant		1	NM_054012.4	P1
ASS1	ENST00000372393.7	c.1127+1973A>G		intron_variant		5		P1
ASS1	ENST00000372394.5	c.1127+1973A>G		intron_variant		2		P1
ASS1	ENST00000372386.6	n.398+1973A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.129

Alfa AF: 0.128 Hom.: 1930

Bravo AF: 0.126

Asia WGS AF: 0.329 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.2
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs544701; hg19: chr9-133372383;