Variant 9-130451924-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_054012.4(ASS1):c.-5-300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 563,280 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 15 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 7 hom. )

Consequence

ASS1
NM_054012.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0310

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 9-130451924-G-A is Benign according to our data. Variant chr9-130451924-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1204545.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00677 (1032/152334) while in subpopulation AFR AF= 0.0237 (985/41576). AF 95% confidence interval is 0.0225. There are 15 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4 linkuse as main transcript	c.-5-300G>A		intron_variant		ENST00000352480.10
ASS1	NM_000050.4 linkuse as main transcript	c.-5-300G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
ASS1	ENST00000352480.10 linkuse as main transcript	c.-5-300G>A	intron_variant		1	NM_054012.4	P1
ASS1	ENST00000372394.5 linkuse as main transcript	c.-125G>A	5_prime_UTR_variant	2/16	2		P1
ASS1	ENST00000372393.7 linkuse as main transcript	c.-5-300G>A	intron_variant		5		P1
ASS1	ENST00000422569.5 linkuse as main transcript	c.-5-300G>A	intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00677

AC:

1031

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00159

AC:

214

AN:

134696

Hom.:

AF XY:

0.00132

AC XY:

AN XY:

73336

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000190

Gnomad SAS exome

AF:

0.0000445

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000170

Gnomad OTH exome

AF:

0.000482

GnomAD4 exome

AF:

0.00102

AC:

418

AN:

410946

Hom.:

Cov.:

AF XY:

0.000816

AC XY:

185

AN XY:

226830

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000107

Gnomad4 SAS exome

AF:

0.0000659

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000920

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00677

AC:

1032

AN:

152334

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

492

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0237

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.00773

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.46

DANN

Benign

0.74

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