chr7-97869013-G-A

Variant names:

• chr7-97869013-G-A
• rs11554431
• NM_001673.5:c.144C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001673.5(ASNS):​c.144C>T​(p.His48His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,614,170 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (4 hom.)
• Consequence: ASNS NM_001673.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.408
• Publications: 1 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ENSG00000284707 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 7-97869013-G-A is Benign according to our data. Variant chr7-97869013-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.408 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00246 (375/152282) while in subpopulation AFR AF = 0.00859 (357/41544). AF 95% confidence interval is 0.00786. There are 2 homozygotes in GnomAd4. There are 179 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASNS	NM_001673.5	MANE Select	c.144C>T	p.His48His	synonymous	Exon 3 of 13	NP_001664.3
	ASNS	NM_001352496.2		c.144C>T	p.His48His	synonymous	Exon 4 of 14	NP_001339425.1	P08243-1
	ASNS	NM_133436.3		c.144C>T	p.His48His	synonymous	Exon 3 of 13	NP_597680.2	P08243-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASNS	ENST00000394308.8	TSL:1 MANE Select	c.144C>T	p.His48His	synonymous	Exon 3 of 13	ENSP00000377845.3	P08243-1
	ASNS	ENST00000175506.8	TSL:1	c.144C>T	p.His48His	synonymous	Exon 4 of 14	ENSP00000175506.4	P08243-1
	ASNS	ENST00000931349.1		c.144C>T	p.His48His	synonymous	Exon 3 of 13	ENSP00000601408.1

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 373 AN: 152164 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00857

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000652 AC: 164 AN: 251462 AF XY: 0.000464

Gnomad AFR exome AF: 0.00947

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000227 AC: 332 AN: 1461888 Hom.: 4 Cov.: 31 AF XY: 0.000182 AC XY: 132 AN XY: 727246

African (AFR) AF: 0.00863 AC: 289 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112012

Other (OTH) AF: 0.000381 AC: 23 AN: 60396

GnomAD4 genome AF: 0.00246 AC: 375 AN: 152282 Hom.: 2 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74464

African (AFR) AF: 0.00859 AC: 357 AN: 41544

American (AMR) AF: 0.000916 AC: 14 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.000953 Hom.: 0

Bravo AF: 0.00268

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ASNS-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.4
DANN	Benign	0.84
PhyloP100		0.41
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11554431; hg19: chr7-97498325;