rs117035302

Positions:

chr7-66087805-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000048.4(ASL):c.718+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,614,052 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 62 hom., cov: 32)

Exomes 𝑓: 0.011 ( 446 hom. )

Consequence

ASL
NM_000048.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.329

Variant links:

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]

ASL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-66087805-A-T is Benign according to our data. Variant chr7-66087805-A-T is described in ClinVar as [Benign]. Clinvar id is 254742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-66087805-A-T is described in Lovd as [Benign]. Variant chr7-66087805-A-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ASL	NM_000048.4 linkuse as main transcript	c.718+14A>T	intron_variant	ENST00000304874.14
ASL	NM_001024943.2 linkuse as main transcript	c.718+14A>T	intron_variant
ASL	NM_001024944.2 linkuse as main transcript	c.718+14A>T	intron_variant
ASL	NM_001024946.2 linkuse as main transcript	c.640+14A>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASL	ENST00000304874.14 linkuse as main transcript	c.718+14A>T		intron_variant		1	NM_000048.4	P1	P04424-1

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2515

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00879

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0926

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.0755

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00566

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0226

AC:

5676

AN:

251186

Hom.:

142

AF XY:

0.0205

AC XY:

2785

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00997

Gnomad AMR exome

AF:

0.0403

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.0868

Gnomad SAS exome

AF:

0.00523

Gnomad FIN exome

AF:

0.0677

Gnomad NFE exome

AF:

0.00612

Gnomad OTH exome

AF:

0.0241

GnomAD4 exome

AF:

0.0108

AC:

15726

AN:

1461802

Hom.:

446

Cov.:

AF XY:

0.0105

AC XY:

7614

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.00583

Gnomad4 FIN exome

AF:

0.0693

Gnomad4 NFE exome

AF:

0.00368

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0166

AC:

2527

AN:

152250

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1458

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.0247

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.0926

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.0755

Gnomad4 NFE

AF:

0.00566

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.0132

Asia WGS

AF:

0.0720

AC:

250

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 17, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Argininosuccinate lyase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over