7-97858834-GT-GTTT

Position:

• chr7-97858834-GT-GTTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001673.5(ASNS):​c.775+19_775+20insAA 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

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]

CZ1P-ASNS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASNS	NM_001673.5	c.775+19_775+20insAA		intron_variant		ENST00000394308.8	NP_001664.3
CZ1P-ASNS	NR_147989.1	n.2404+19_2404+20insAA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASNS	ENST00000394308.8	c.775+19_775+20insAA		intron_variant		1	NM_001673.5	ENSP00000377845	P1

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

GnomAD3 exomes AF: 0.0112 AC: 2629 AN: 233956 Hom.: 60 AF XY: 0.0113 AC XY: 1428 AN XY: 126490

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 SAS exome AF: 0.00604

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

Gnomad4 AFR exome AF: 0.000964

Gnomad4 AMR exome AF: 0.00216

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.00592

Gnomad4 FIN exome AF: 0.0581

Gnomad4 NFE exome AF: 0.00873

Gnomad4 OTH exome AF: 0.00708

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

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00561

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.00927

Gnomad4 OTH AF: 0.00474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 24, 2017	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36021744; hg19: chr7-97488146;