Variant chr9-130452052-T-C 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.-5-172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 700,902 control chromosomes in the GnomAD database, including 330,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68584 hom., cov: 32)

Exomes 𝑓: 0.98 ( 262034 hom. )

Consequence

ASS1
NM_054012.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.15

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:

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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=-0.71).

BP6

Variant 9-130452052-T-C is Benign according to our data. Variant chr9-130452052-T-C is described in ClinVar as [Benign]. Clinvar id is 683297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4 linkuse as main transcript	c.-5-172T>C		intron_variant		ENST00000352480.10
ASS1	NM_000050.4 linkuse as main transcript	c.-5-172T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ASS1	ENST00000352480.10 linkuse as main transcript	c.-5-172T>C	intron_variant	1	NM_054012.4	P1
ASS1	ENST00000372393.7 linkuse as main transcript	c.-5-172T>C	intron_variant	5		P1
ASS1	ENST00000372394.5 linkuse as main transcript	c.-6+9T>C	intron_variant	2		P1
ASS1	ENST00000422569.5 linkuse as main transcript	c.-5-172T>C	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.947

AC:

144125

AN:

152122

Hom.:

68533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.975

Gnomad ASJ

AF:

0.949

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.971

Gnomad FIN

AF:

0.964

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.985

Gnomad OTH

AF:

0.955

GnomAD3 exomes

AF:

0.974

AC:

136120

AN:

139790

Hom.:

66339

AF XY:

0.974

AC XY:

73312

AN XY:

75276

show subpopulations

Gnomad AFR exome

AF:

0.855

Gnomad AMR exome

AF:

0.986

Gnomad ASJ exome

AF:

0.959

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.964

Gnomad FIN exome

AF:

0.968

Gnomad NFE exome

AF:

0.985

Gnomad OTH exome

AF:

0.974

GnomAD4 exome

AF:

0.977

AC:

536039

AN:

548662

Hom.:

262034

Cov.:

AF XY:

0.977

AC XY:

290060

AN XY:

296822

show subpopulations

Gnomad4 AFR exome

AF:

0.857

Gnomad4 AMR exome

AF:

0.985

Gnomad4 ASJ exome

AF:

0.958

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.965

Gnomad4 FIN exome

AF:

0.969

Gnomad4 NFE exome

AF:

0.985

Gnomad4 OTH exome

AF:

0.972

GnomAD4 genome

AF:

0.947

AC:

144233

AN:

152240

Hom.:

68584

Cov.:

AF XY:

0.947

AC XY:

70512

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.860

Gnomad4 AMR

AF:

0.975

Gnomad4 ASJ

AF:

0.949

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.971

Gnomad4 FIN

AF:

0.964

Gnomad4 NFE

AF:

0.985

Gnomad4 OTH

AF:

0.956

Alfa

AF:

0.955

Hom.:

8580

Bravo

AF:

0.944

Asia WGS

AF:

0.979

AC:

3405

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Citrullinemia type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.1

DANN

Benign

0.80

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