7-66081579-CAAAA-CAAAAA

Variant names:

• chr7-66081579-C-CA
• rs113517237
• NM_000048.4:c.13-209dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000048.4(ASL):​c.13-209dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 115,152 control chromosomes in the GnomAD database, including 61 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.019 (61 hom., cov: 31)
• Consequence: ASL NM_000048.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581

Genes affected

ASL (HGNC:746): (argininosuccinate lyase) This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASL	NM_000048.4	c.13-209dupA		intron_variant	Intron 2 of 16	ENST00000304874.14	NP_000039.2
ASL	NM_001024943.2	c.13-209dupA		intron_variant	Intron 1 of 15		NP_001020114.1
ASL	NM_001024944.2	c.13-209dupA		intron_variant	Intron 1 of 14		NP_001020115.1
ASL	NM_001024946.2	c.13-209dupA		intron_variant	Intron 1 of 14		NP_001020117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASL	ENST00000304874.14	c.13-224_13-223insA		intron_variant	Intron 2 of 16	1	NM_000048.4	ENSP00000307188.9

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2182 AN: 115128 Hom.: 60 Cov.: 31

Gnomad AFR AF: 0.00491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.00768

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00780

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0190 AC: 2193 AN: 115152 Hom.: 61 Cov.: 31 AF XY: 0.0226 AC XY: 1239 AN XY: 54752

Gnomad4 AFR AF: 0.00500

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.00768

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0987

Gnomad4 NFE AF: 0.00780

Gnomad4 OTH AF: 0.0316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs113517237; hg19: chr7-65546566;