chr7-66081579-C-CA

Variant names:

• chr7-66081579-C-CA
• rs113517237
• NM_000048.4:c.13-209dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000048.4(ASL):​c.13-209dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 115,152 control chromosomes in the GnomAD database, including 61 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.019 (61 hom., cov: 31)
• Consequence: ASL NM_000048.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 0 publications found

Genes affected

ASL (HGNC:746): (argininosuccinate lyase) This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ASL Gene-Disease associations (from GenCC):

• argininosuccinic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000048.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASL	NM_000048.4	MANE Select	c.13-209dupA		intron	N/A	NP_000039.2
	ASL	NM_001024943.2		c.13-209dupA		intron	N/A	NP_001020114.1	A0A024RDL8
	ASL	NM_001024944.2		c.13-209dupA		intron	N/A	NP_001020115.1	P04424-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASL	ENST00000304874.14	TSL:1 MANE Select	c.13-224_13-223insA		intron	N/A	ENSP00000307188.9	P04424-1
	ASL	ENST00000395332.8	TSL:1	c.13-224_13-223insA		intron	N/A	ENSP00000378741.3	P04424-1
	ASL	ENST00000496336.1	TSL:1	n.254-224_254-223insA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2182 AN: 115128 Hom.: 60 Cov.: 31

Gnomad AFR AF: 0.00491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.00768

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00780

Gnomad OTH AF: 0.0272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0190 AC: 2193 AN: 115152 Hom.: 61 Cov.: 31 AF XY: 0.0226 AC XY: 1239 AN XY: 54752

African (AFR) AF: 0.00500 AC: 153 AN: 30618

American (AMR) AF: 0.0338 AC: 367 AN: 10868

Ashkenazi Jewish (ASJ) AF: 0.00768 AC: 22 AN: 2864

East Asian (EAS) AF: 0.115 AC: 482 AN: 4176

South Asian (SAS) AF: 0.0122 AC: 44 AN: 3606

European-Finnish (FIN) AF: 0.0987 AC: 654 AN: 6624

Middle Eastern (MID) AF: 0.0135 AC: 3 AN: 222

European-Non Finnish (NFE) AF: 0.00780 AC: 421 AN: 53982

Other (OTH) AF: 0.0316 AC: 47 AN: 1488

Alfa AF: 0.00514 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs113517237; hg19: chr7-65546566;