7-97872310-TGGCGCGGGGCGCAG-TGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAG

Variant names:

• chr7-97872310-T-TGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAG
• rs3832526
• NM_001673.5:c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 8 publications found

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

ENSG00000297732 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001673.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASNS	NM_001673.5	MANE Select	c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	NP_001664.3
	ASNS	NM_001352496.2		c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	NP_001339425.1
	ASNS	NM_183356.4		c.-338+40_-338+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	NP_899199.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASNS	ENST00000394308.8	TSL:1 MANE Select	c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	ENSP00000377845.3
	ASNS	ENST00000175506.8	TSL:1	c.-338+40_-338+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	ENSP00000175506.4
	ENSG00000297732	ENST00000750621.1		n.123_124insGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000632 AC: 95 AN: 150388 Hom.: 1 Cov.: 31

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.: 0

GnomAD4 genome AF: 0.000631 AC: 95 AN: 150506 Hom.: 1 Cov.: 31 AF XY: 0.000625 AC XY: 46 AN XY: 73590

African (AFR) AF: 0.00200 AC: 80 AN: 40080

American (AMR) AF: 0.000328 AC: 5 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000978 AC: 5 AN: 5110

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67904

Other (OTH) AF: 0.00143 AC: 3 AN: 2096

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs3832526; hg19: chr7-97501622;