Variant 7-66076198-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.303

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:

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ACMG classification

Classification made for transcript

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	Effect	MANE
ASL	NM_000048.4 linkuse as main transcript	c.12+105C>T	intron_variant	ENST00000304874.14
ASL	NM_001024943.2 linkuse as main transcript	c.12+105C>T	intron_variant
ASL	NM_001024944.2 linkuse as main transcript	c.12+105C>T	intron_variant
ASL	NM_001024946.2 linkuse as main transcript	c.12+105C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASL	ENST00000304874.14 linkuse as main transcript	c.12+105C>T		intron_variant		1	NM_000048.4	P1	P04424-1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90845

AN:

151928

Hom.:

27686

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.594

AC XY:

44127

AN XY:

74330

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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