Genetic Variant NM_001673.5:c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC (chr7-97872310-T-TGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001673.5(ASNS):c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 150,506 control chromosomes in the GnomAD database, including 1 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 0.00063 ( 1 hom., cov: 31)

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: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000631 (95/150506) while in subpopulation AFR AF = 0.002 (80/40080). AF 95% confidence interval is 0.00164. There are 1 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNS	NM_001673.5 link	c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC		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+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron_variant	Intron 1 of 12	1	NM_001673.5	ENSP00000377845.3		P08243-1

Frequencies

GnomAD3 genomes

AF:

0.000632

AC:

AN:

150388

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000976

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00145

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.000631

AC:

AN:

150506

Hom.:

Cov.:

AF XY:

0.000625

AC XY:

AN XY:

73590

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

40080

American (AMR)

AF:

0.000328

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.000978

AC:

AN:

5110

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67904

Other (OTH)

AF:

0.00143

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.81

Splicing

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

Publications

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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