4-139695263-C-T

Variant names:

• chr4-139695263-C-T
• rs8192098
• NM_002413.5:c.225C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002413.5(MGST2):​c.225C>T​(p.Asn75Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 1,607,104 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (23 hom.)
• Consequence: MGST2 NM_002413.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.257
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 4-139695263-C-T is Benign according to our data. Variant chr4-139695263-C-T is described in ClinVar as Benign. ClinVar VariationId is 710321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.257 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002413.5. 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
	MGST2	NM_002413.5	MANE Select	c.225C>T	p.Asn75Asn	synonymous	Exon 3 of 5	NP_002404.1	Q99735-1
	MGST2	NM_001204366.2		c.225C>T	p.Asn75Asn	synonymous	Exon 3 of 6	NP_001191295.1	Q99735-1
	MGST2	NM_001204367.2		c.21C>T	p.Asn7Asn	synonymous	Exon 2 of 5	NP_001191296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST2	ENST00000265498.6	TSL:1 MANE Select	c.225C>T	p.Asn75Asn	synonymous	Exon 3 of 5	ENSP00000265498.1	Q99735-1
	MGST2	ENST00000515137.5	TSL:1	n.212C>T		non_coding_transcript_exon	Exon 2 of 5
	MGST2	ENST00000899649.1		c.318C>T	p.Asn106Asn	synonymous	Exon 4 of 6	ENSP00000569708.1

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 151978 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00152

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00497

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00329 AC: 826 AN: 251412 AF XY: 0.00336

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00590

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00491 AC: 7142 AN: 1455008 Hom.: 23 Cov.: 28 AF XY: 0.00487 AC XY: 3528 AN XY: 724448

African (AFR) AF: 0.000720 AC: 24 AN: 33336

American (AMR) AF: 0.00130 AC: 58 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00115 AC: 99 AN: 86100

European-Finnish (FIN) AF: 0.00213 AC: 114 AN: 53410

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5756

European-Non Finnish (NFE) AF: 0.00599 AC: 6620 AN: 1105744

Other (OTH) AF: 0.00344 AC: 207 AN: 60194

GnomAD4 genome AF: 0.00290 AC: 441 AN: 152096 Hom.: 2 Cov.: 32 AF XY: 0.00262 AC XY: 195 AN XY: 74328

African (AFR) AF: 0.000940 AC: 39 AN: 41502

American (AMR) AF: 0.00236 AC: 36 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00152 AC: 16 AN: 10540

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00497 AC: 338 AN: 68010

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00461 Hom.: 9

Bravo AF: 0.00295

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00671

EpiControl AF: 0.00581

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	4.4
DANN	Benign	0.80
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs8192098; hg19: chr4-140616417; COSMIC: COSV108014819;