chr9-130445062-A-C

Position:

• chr9-130445062-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_054012.4(ASS1):​c.-6+67A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 764,986 control chromosomes in the GnomAD database, including 106,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20706 hom., cov: 34)
  • Exomes 𝑓: 0.53 (85466 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.420

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-130445062-A-C is Benign according to our data. Variant chr9-130445062-A-C is described in ClinVar as [Benign]. Clinvar id is 1249407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.-6+67A>C		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.-68+67A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.-6+67A>C		intron_variant		1	NM_054012.4	P1
ASS1	ENST00000422569.5	c.-142A>C		5_prime_UTR_variant	1/8	5
ASS1	ENST00000372393.7	c.-68+67A>C		intron_variant		5		P1
ASS1	ENST00000372394.5	c.-448+67A>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79097 AN: 151980 Hom.: 20673 Cov.: 34

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.527 AC: 323065 AN: 612890 Hom.: 85466 Cov.: 7 AF XY: 0.528 AC XY: 151160 AN XY: 286540

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.589

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.521 AC: 79189 AN: 152096 Hom.: 20706 Cov.: 34 AF XY: 0.519 AC XY: 38585 AN XY: 74356

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.505

Alfa AF: 0.502 Hom.: 2979

Bravo AF: 0.523

Asia WGS AF: 0.517 AC: 1796 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs6597680; hg19: chr9-133320449;