chr7-97858834-G-GTT

Variant names:

• chr7-97858834-G-GTT
• rs36021744
• NM_001673.5:c.775+18_775+19dupAA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001673.5(ASNS):​c.775+18_775+19dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00962 in 1,587,228 control chromosomes in the GnomAD database, including 184 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (20 hom., cov: 21)
  • Exomes 𝑓: 0.0096 (164 hom.)
• Consequence: ASNS NM_001673.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0440
• Publications: 2 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

ENSG00000284707 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-97858834-G-GTT is Benign according to our data. Variant chr7-97858834-G-GTT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00996 (1514/152062) while in subpopulation NFE AF = 0.00927 (630/67984). AF 95% confidence interval is 0.00867. There are 20 homozygotes in GnomAd4. There are 894 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNS	NM_001673.5	c.775+18_775+19dupAA		intron_variant	Intron 6 of 12	ENST00000394308.8	NP_001664.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASNS	ENST00000394308.8	c.775+19_775+20insAA		intron_variant	Intron 6 of 12	1	NM_001673.5	ENSP00000377845.3

Frequencies

GnomAD3 genomes AF: 0.00996 AC: 1513 AN: 151944 Hom.: 20 Cov.: 21

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00927

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.0112 AC: 2629 AN: 233956 AF XY: 0.0113

Gnomad AFR exome AF: 0.00144

Gnomad AMR exome AF: 0.00219

Gnomad ASJ exome AF: 0.00133

Gnomad EAS exome AF: 0.000402

Gnomad FIN exome AF: 0.0612

Gnomad NFE exome AF: 0.00917

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.00959 AC: 13758 AN: 1435166 Hom.: 164 Cov.: 30 AF XY: 0.00959 AC XY: 6849 AN XY: 714324

African (AFR) AF: 0.000964 AC: 31 AN: 32150

American (AMR) AF: 0.00216 AC: 85 AN: 39334

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 30 AN: 25240

East Asian (EAS) AF: 0.000329 AC: 13 AN: 39472

South Asian (SAS) AF: 0.00592 AC: 486 AN: 82130

European-Finnish (FIN) AF: 0.0581 AC: 3087 AN: 53096

Middle Eastern (MID) AF: 0.00214 AC: 12 AN: 5610

European-Non Finnish (NFE) AF: 0.00873 AC: 9594 AN: 1098798

Other (OTH) AF: 0.00708 AC: 420 AN: 59336

GnomAD4 genome AF: 0.00996 AC: 1514 AN: 152062 Hom.: 20 Cov.: 21 AF XY: 0.0120 AC XY: 894 AN XY: 74330

African (AFR) AF: 0.00152 AC: 63 AN: 41482

American (AMR) AF: 0.00379 AC: 58 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00561 AC: 27 AN: 4812

European-Finnish (FIN) AF: 0.0633 AC: 668 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00927 AC: 630 AN: 67984

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00511 Hom.: 663

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs36021744; hg19: chr7-97488146;