7-97872310-TGGCGCGGGGCGCAG-TGGCGCGGGGCGCAGGGCGCGGGGCGCAGGGCGCGGGGCGCAG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001673.5(ASNS):​c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 151,450 control chromosomes in the GnomAD database, including 3 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 0.0032 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (1 hom.)
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00322 (485/150510) while in subpopulation AFR AF = 0.00776 (311/40084). AF 95% confidence interval is 0.00705. There are 2 homozygotes in GnomAd4. There are 244 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	NP_001664.3
	ASNS	NM_001352496.2		c.-60+40_-60+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	NP_001339425.1
	ASNS	NM_183356.4		c.-338+40_-338+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCC		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+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	ENSP00000377845.3
	ASNS	ENST00000175506.8	TSL:1	c.-338+40_-338+41insCTGCGCCCCGCGCCCTGCGCCCCGCGCC		intron	N/A	ENSP00000175506.4
	ENSG00000297732	ENST00000750621.1		n.123_124insGCGGGGCGCAGGGCGCGGGGCGCAGGGC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 486 AN: 150392 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00375

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00781

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000795

Gnomad OTH AF: 0.00338

GnomAD4 exome AF: 0.00426 AC: 4 AN: 940 Hom.: 1 Cov.: 0 AF XY: 0.00142 AC XY: 1 AN XY: 706

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.0250 AC: 1 AN: 40

South Asian (SAS) AF: 0.0833 AC: 2 AN: 24

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00125 AC: 1 AN: 798

Other (OTH) AF: 0.00 AC: 0 AN: 32

GnomAD4 genome AF: 0.00322 AC: 485 AN: 150510 Hom.: 2 Cov.: 31 AF XY: 0.00332 AC XY: 244 AN XY: 73594

African (AFR) AF: 0.00776 AC: 311 AN: 40084

American (AMR) AF: 0.00374 AC: 57 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3460

East Asian (EAS) AF: 0.00744 AC: 38 AN: 5110

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000795 AC: 54 AN: 67904

Other (OTH) AF: 0.00334 AC: 7 AN: 2096

Alfa AF: 0.0000656 Hom.: 13

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;