Variant 9-130480487-A-G 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_054012.4(ASS1):c.838+38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,608,404 control chromosomes in the GnomAD database, including 776,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 63805 hom., cov: 35)

Exomes 𝑓: 0.99 ( 712503 hom. )

Consequence

ASS1
NM_054012.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.580

Variant links:

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]

ASS1 links:

ASS1 (HGNC:):

ASS1 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=-0.88).

BP6

Variant 9-130480487-A-G is Benign according to our data. Variant chr9-130480487-A-G is described in ClinVar as [Benign]. Clinvar id is 254749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-130480487-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASS1	NM_054012.4 linkuse as main transcript	c.838+38A>G		intron_variant		ENST00000352480.10	NP_446464.1	P00966Q5T6L4
ASS1	NM_000050.4 linkuse as main transcript	c.838+38A>G		intron_variant			NP_000041.2	P00966Q5T6L4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10 linkuse as main transcript	c.838+38A>G		intron_variant		1	NM_054012.4	ENSP00000253004.6		P00966

Frequencies

GnomAD3 genomes

AF:

0.905

AC:

137638

AN:

152152

Hom.:

63771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.959

Gnomad ASJ

AF:

0.965

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.996

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.925

GnomAD3 exomes

AF:

0.973

AC:

238465

AN:

245134

Hom.:

116773

AF XY:

0.979

AC XY:

129950

AN XY:

132686

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.982

Gnomad ASJ exome

AF:

0.969

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.997

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.997

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.988

AC:

1438498

AN:

1456134

Hom.:

712503

Cov.:

AF XY:

0.989

AC XY:

716522

AN XY:

724340

show subpopulations

Gnomad4 AFR exome

AF:

0.659

Gnomad4 AMR exome

AF:

0.980

Gnomad4 ASJ exome

AF:

0.969

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.998

Gnomad4 OTH exome

AF:

0.973

GnomAD4 genome

AF:

0.904

AC:

137727

AN:

152270

Hom.:

63805

Cov.:

AF XY:

0.908

AC XY:

67592

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.677

Gnomad4 AMR

AF:

0.959

Gnomad4 ASJ

AF:

0.965

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.996

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.926

Alfa

AF:

0.943

Hom.:

13946

Bravo

AF:

0.889

Asia WGS

AF:

0.984

AC:

3421

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	-	- -

Citrullinemia type I

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 06, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.1

DANN

Benign

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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