Variant 9-130452009-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_054012.4(ASS1):c.-5-215G>A 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 677,806 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 10 hom., cov: 33)

Exomes 𝑓: 0.012 ( 80 hom. )

Consequence

ASS1
NM_054012.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.351

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:

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=-0.64).

BP6

Variant 9-130452009-G-A is Benign according to our data. Variant chr9-130452009-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0118 (6177/525474) while in subpopulation MID AF= 0.0206 (81/3928). AF 95% confidence interval is 0.017. There are 80 homozygotes in gnomad4_exome. There are 3245 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASS1	NM_054012.4 linkuse as main transcript	c.-5-215G>A		intron_variant		ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4 linkuse as main transcript	c.-5-215G>A		intron_variant			NP_000041.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ASS1	ENST00000352480.10 linkuse as main transcript	c.-5-215G>A	intron_variant		1	NM_054012.4	ENSP00000253004	P1
ASS1	ENST00000372394.5 linkuse as main transcript	c.-40G>A	5_prime_UTR_variant	2/16	2		ENSP00000361471	P1
ASS1	ENST00000372393.7 linkuse as main transcript	c.-5-215G>A	intron_variant		5		ENSP00000361469	P1
ASS1	ENST00000422569.5 linkuse as main transcript	c.-5-215G>A	intron_variant		5		ENSP00000394212

Frequencies

GnomAD3 genomes

AF:

0.00959

AC:

1459

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00603

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0113

AC:

1546

AN:

136468

Hom.:

AF XY:

0.0112

AC XY:

827

AN XY:

74076

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.00749

Gnomad ASJ exome

AF:

0.0512

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00331

Gnomad FIN exome

AF:

0.00905

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0118

AC:

6177

AN:

525474

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

3245

AN XY:

285182

show subpopulations

Gnomad4 AFR exome

AF:

0.00237

Gnomad4 AMR exome

AF:

0.00765

Gnomad4 ASJ exome

AF:

0.0496

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.00318

Gnomad4 FIN exome

AF:

0.00576

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.00958

AC:

1459

AN:

152332

Hom.:

Cov.:

AF XY:

0.00937

AC XY:

698

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00603

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.00992

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.8

DANN

Benign

0.62

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