rs2132845

Positions:

• chr4-139665971-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002413.5(MGST2):​c.-49A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 1,594,494 control chromosomes in the GnomAD database, including 7,699 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 0.12 (1676 hom., cov: 31)
  • Exomes 𝑓: 0.080 (6023 hom.)
• Consequence: MGST2 NM_002413.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

MGST2 (HGNC:7063): (microsomal glutathione S-transferase 2) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, several of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes a protein which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGST2	NM_002413.5	c.-49A>T		5_prime_UTR_variant	1/5	ENST00000265498.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGST2	ENST00000265498.6	c.-49A>T		5_prime_UTR_variant	1/5	1	NM_002413.5	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18836 AN: 151964 Hom.: 1676 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.0900 AC: 22477 AN: 249792 Hom.: 1478 AF XY: 0.0894 AC XY: 12066 AN XY: 134970

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.0409

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.0393

Gnomad NFE exome AF: 0.0688

Gnomad OTH exome AF: 0.0824

GnomAD4 exome AF: 0.0797 AC: 114999 AN: 1442412 Hom.: 6023 Cov.: 27 AF XY: 0.0811 AC XY: 58284 AN XY: 718688

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.0457

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0392

Gnomad4 NFE exome AF: 0.0680

Gnomad4 OTH exome AF: 0.0974

GnomAD4 genome AF: 0.124 AC: 18846 AN: 152082 Hom.: 1676 Cov.: 31 AF XY: 0.123 AC XY: 9114 AN XY: 74364

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0766

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0413

Gnomad4 NFE AF: 0.0682

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0852 Hom.: 457

Bravo AF: 0.132

Asia WGS AF: 0.152 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2132845; hg19: chr4-140587125; COSMIC: COSV55497492; COSMIC: COSV55497492;