chr9-130445039-G-C

Position:

• chr9-130445039-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_054012.4(ASS1):​c.-6+44G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 576,392 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (21 hom., cov: 33)
  • Exomes 𝑓: 0.020 (91 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.733

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=-0.78).
• BP6: Variant 9-130445039-G-C is Benign according to our data. Variant chr9-130445039-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1328790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0126 (1925/152346) while in subpopulation NFE AF= 0.0205 (1398/68032). AF 95% confidence interval is 0.0197. There are 21 homozygotes in gnomad4. There are 905 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.-6+44G>C		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.-68+44G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.-6+44G>C		intron_variant		1	NM_054012.4	P1
ASS1	ENST00000422569.5	c.-165G>C		5_prime_UTR_variant	1/8	5
ASS1	ENST00000372393.7	c.-68+44G>C		intron_variant		5		P1
ASS1	ENST00000372394.5	c.-448+44G>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1925 AN: 152228 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00477

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.00909

GnomAD4 exome AF: 0.0203 AC: 8601 AN: 424046 Hom.: 91 Cov.: 5 AF XY: 0.0204 AC XY: 4087 AN XY: 199972

Gnomad4 AFR exome AF: 0.00241

Gnomad4 AMR exome AF: 0.00652

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.00833

Gnomad4 NFE exome AF: 0.0210

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0126 AC: 1925 AN: 152346 Hom.: 21 Cov.: 33 AF XY: 0.0121 AC XY: 905 AN XY: 74500

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.0155 Hom.: 0

Bravo AF: 0.0113

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jun 17, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.2
DANN	Benign	0.45

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: rs151254686; hg19: chr9-133320426;