4-139665971-A-T

Variant names:

• chr4-139665971-A-T
• rs2132845
• ENST00000515137.5:n.39A>T

Variant summary

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

The ENST00000515137.5(MGST2):​n.39A>T variant causes a non coding transcript exon 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 ENST00000515137.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 19 publications found

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]

QKILA (HGNC:55255): (QKI interacting lncRNA)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515137.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST2	NM_002413.5	MANE Select	c.-49A>T		5_prime_UTR	Exon 1 of 5	NP_002404.1
	MGST2	NM_001204366.2		c.-49A>T		5_prime_UTR	Exon 1 of 6	NP_001191295.1
	MGST2	NM_001204367.2		c.-153A>T		5_prime_UTR	Exon 1 of 5	NP_001191296.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST2	ENST00000515137.5	TSL:1	n.39A>T		non_coding_transcript_exon	Exon 1 of 5
	MGST2	ENST00000265498.6	TSL:1 MANE Select	c.-49A>T		5_prime_UTR	Exon 1 of 5	ENSP00000265498.1
	QKILA	ENST00000730152.1		n.98T>A		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.0900 AC: 22477 AN: 249792 AF XY: 0.0894

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 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

African (AFR) AF: 0.258 AC: 8558 AN: 33140

American (AMR) AF: 0.0457 AC: 2040 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3315 AN: 25998

East Asian (EAS) AF: 0.195 AC: 7739 AN: 39602

South Asian (SAS) AF: 0.121 AC: 10325 AN: 85562

European-Finnish (FIN) AF: 0.0392 AC: 2093 AN: 53376

Middle Eastern (MID) AF: 0.110 AC: 628 AN: 5714

European-Non Finnish (NFE) AF: 0.0680 AC: 74483 AN: 1094660

Other (OTH) AF: 0.0974 AC: 5818 AN: 59756

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

African (AFR) AF: 0.251 AC: 10385 AN: 41432

American (AMR) AF: 0.0766 AC: 1170 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3470

East Asian (EAS) AF: 0.164 AC: 847 AN: 5172

South Asian (SAS) AF: 0.122 AC: 587 AN: 4820

European-Finnish (FIN) AF: 0.0413 AC: 438 AN: 10594

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0682 AC: 4639 AN: 68004

Other (OTH) AF: 0.112 AC: 237 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		2.0
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=297/3	polymorphism (auto)

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

Other links and lift over

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