rs3757676

Variant names:

• chr7-97872723-G-A
• rs3757676
• NM_001352496.2:c.-158-274C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352496.2(ASNS):​c.-158-274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,150 control chromosomes in the GnomAD database, including 10,382 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10382 hom., cov: 34)
• Consequence: ASNS NM_001352496.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNS	NM_001352496.2	c.-158-274C>T		intron_variant	Intron 1 of 13		NP_001339425.1
CZ1P-ASNS	NR_147989.1	n.1571-2910C>T		intron_variant	Intron 7 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284707	ENST00000641315.1	n.331-3647C>T		intron_variant	Intron 1 of 11
ENSG00000284707	ENST00000641390.1	n.797-274C>T		intron_variant	Intron 5 of 17
ENSG00000284707	ENST00000641784.1	n.1329-274C>T		intron_variant	Intron 5 of 17

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55151 AN: 152032 Hom.: 10358 Cov.: 34

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55224 AN: 152150 Hom.: 10382 Cov.: 34 AF XY: 0.366 AC XY: 27197 AN XY: 74382

African (AFR) AF: 0.457 AC: 18983 AN: 41506

American (AMR) AF: 0.309 AC: 4730 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2305 AN: 5174

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4822

European-Finnish (FIN) AF: 0.379 AC: 4011 AN: 10582

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21391 AN: 67976

Other (OTH) AF: 0.371 AC: 785 AN: 2114

Alfa AF: 0.356 Hom.: 1232

Bravo AF: 0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-1.0
PromoterAI		-0.036	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3757676; hg19: chr7-97502035;