Variant 9-130450341-C-T 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.-5-1883C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 987,336 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 26 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 12 hom. )

Consequence

ASS1
NM_054012.4 intron

Scores

Splicing: ADA: 0.00001812

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.296

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 9-130450341-C-T is Benign according to our data. Variant chr9-130450341-C-T is described in ClinVar as [Benign]. Clinvar id is 381450.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1532/152318) while in subpopulation AFR AF= 0.0346 (1437/41562). AF 95% confidence interval is 0.0331. There are 26 homozygotes in gnomad4. There are 730 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4 linkuse as main transcript	c.-5-1883C>T		intron_variant		ENST00000352480.10
ASS1	NM_000050.4 linkuse as main transcript	c.-6+8C>T		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ASS1	ENST00000352480.10 linkuse as main transcript	c.-5-1883C>T	intron_variant	1	NM_054012.4	P1
ASS1	ENST00000372393.7 linkuse as main transcript	c.-6+8C>T	splice_region_variant, intron_variant	5		P1
ASS1	ENST00000372394.5 linkuse as main transcript	c.-447-1261C>T	intron_variant	2		P1
ASS1	ENST00000422569.5 linkuse as main transcript	c.-5-1883C>T	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1529

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0346

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.00114

AC:

951

AN:

835018

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

413

AN XY:

385746

show subpopulations

Gnomad4 AFR exome

AF:

0.0368

Gnomad4 AMR exome

AF:

0.00301

Gnomad4 ASJ exome

AF:

0.000194

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000356

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.0101

AC:

1532

AN:

152318

Hom.:

Cov.:

AF XY:

0.00980

AC XY:

730

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0346

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00913

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2015

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

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.7

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.060

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