9-130451924-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

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 -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 GnomAd at 15 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00677 AC: 1031 AN: 152216 Hom.: 15 Cov.: 33

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.: 4 AF XY: 0.00132 AC XY: 97 AN XY: 73336

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.: 7 Cov.: 0 AF XY: 0.000816 AC XY: 185 AN XY: 226830

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.: 15 Cov.: 33 AF XY: 0.00661 AC XY: 492 AN XY: 74486

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.: 0

Bravo AF: 0.00773

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2018

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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

Other links and lift over

dbSNP: rs114084616; hg19: chr9-133327311;