7-66076198-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000048.4(ASL):c.12+105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,451,750 control chromosomes in the GnomAD database, including 244,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27724 hom., cov: 33)
  • Exomes 𝑓: 0.57 (216893 hom.)
• Consequence: ASL NM_000048.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.303

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-66076198-C-T is Benign according to our data. Variant chr7-66076198-C-T is described in ClinVar as [Benign]. Clinvar id is 1177030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASL	NM_000048.4	c.12+105C>T		intron_variant		ENST00000304874.14
ASL	NM_001024943.2	c.12+105C>T		intron_variant
ASL	NM_001024944.2	c.12+105C>T		intron_variant
ASL	NM_001024946.2	c.12+105C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASL	ENST00000304874.14	c.12+105C>T		intron_variant		1	NM_000048.4	P1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90845 AN: 151928 Hom.: 27686 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.575

GnomAD4 exome AF: 0.573 AC: 745152 AN: 1299706 Hom.: 216893 AF XY: 0.569 AC XY: 366299 AN XY: 643758

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.589

Gnomad4 OTH exome AF: 0.559

GnomAD4 genome AF: 0.598 AC: 90939 AN: 152044 Hom.: 27724 Cov.: 33 AF XY: 0.594 AC XY: 44127 AN XY: 74330

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.574

Alfa AF: 0.594 Hom.: 3378

Bravo AF: 0.601

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Argininosuccinate lyase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.9
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs1183245; hg19: chr7-65541185; COSMIC: COSV59189044; COSMIC: COSV59189044;