Genetic Variant ASNS:c.-60+27_-60+40dupCTGCGCCCCGCGCC (chr7-97872310-T-TGGCGCGGGGCGCAG) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001673.5(ASNS):c.-60+27_-60+40dupCTGCGCCCCGCGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,428 control chromosomes in the GnomAD database, including 2,110 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2099 hom., cov: 31)

Exomes 𝑓: 0.13 ( 11 hom. )

Consequence

ASNS
NM_001673.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.809

Publications

8 publications found

Variant links:

Genes affected

ASNS (HGNC:753): (asparagine synthetase (glutamine-hydrolyzing)) The protein encoded by this gene is involved in the synthesis of asparagine. This gene complements a mutation in the temperature-sensitive hamster mutant ts11, which blocks progression through the G1 phase of the cell cycle at nonpermissive temperature. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]

ASNS Gene-Disease associations (from GenCC):

congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ASNS links:

ENSG00000297732 (HGNC:):

ENSG00000297732 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNS	NM_001673.5 link	c.-60+27_-60+40dupCTGCGCCCCGCGCC		intron_variant	Intron 1 of 12	ENST00000394308.8	NP_001664.3	P08243-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASNS	ENST00000394308.8 link	c.-60+27_-60+40dupCTGCGCCCCGCGCC		intron_variant	Intron 1 of 12	1	NM_001673.5	ENSP00000377845.3		P08243-1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23808

AN:

150370

Hom.:

2091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.0896

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.152

GnomAD4 exome

AF:

0.127

AC:

119

AN:

940

Hom.:

Cov.:

AF XY:

0.139

AC XY:

AN XY:

706

show subpopulations

African (AFR)

AF:

0.100

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.400

AC:

AN:

South Asian (SAS)

AF:

0.0833

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.119

AC:

AN:

798

Other (OTH)

AF:

0.0938

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.158

AC:

23836

AN:

150488

Hom.:

2099

Cov.:

AF XY:

0.161

AC XY:

11883

AN XY:

73586

show subpopulations

African (AFR)

AF:

0.185

AC:

7434

AN:

40076

American (AMR)

AF:

0.273

AC:

4148

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

444

AN:

3460

East Asian (EAS)

AF:

0.232

AC:

1186

AN:

5110

South Asian (SAS)

AF:

0.245

AC:

1180

AN:

4824

European-Finnish (FIN)

AF:

0.0896

AC:

950

AN:

10604

Middle Eastern (MID)

AF:

0.106

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.119

AC:

8070

AN:

67896

Other (OTH)

AF:

0.152

AC:

318

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1061

2122

3183

4244

5305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0263

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-97872310-TGGCGCGGGGCGCAG-TGGCGCGGGGCGCAGGGCGCGGGGCGCAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over