1-165655786-G-T

Position:

• chr1-165655786-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004528.4(MGST3):​c.*282G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 446,622 control chromosomes in the GnomAD database, including 19,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (6066 hom., cov: 30)
  • Exomes 𝑓: 0.24 (13802 hom.)
• Consequence: MGST3 NM_004528.4 3_prime_UTR
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: -0.438

Genes affected

MGST3 (HGNC:7064): (microsomal glutathione S-transferase 3) This gene encodes a member of the MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) protein family. Members of this family are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes an enzyme which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. This enzyme also demonstrates glutathione-dependent peroxidase activity towards lipid hydroperoxides.[provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 1-165655786-G-T is Benign according to our data. Variant chr1-165655786-G-T is described in ClinVar as [protective]. Clinvar id is 1693589.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST3	NM_004528.4	c.*282G>T		3_prime_UTR_variant	6/6	ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.*282G>T		3_prime_UTR_variant	7/7		XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST3	ENST00000367889.8	c.*282G>T		3_prime_UTR_variant	6/6	1	NM_004528.4	ENSP00000356864.3
MGST3	ENST00000627653.1	c.*282G>T		3_prime_UTR_variant	6/6	5		ENSP00000487151.1
MGST3	ENST00000367888.8	c.322+1435G>T		intron_variant		3		ENSP00000356863.4

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36761 AN: 151284 Hom.: 6045 Cov.: 30

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.244 AC: 72129 AN: 295220 Hom.: 13802 Cov.: 3 AF XY: 0.254 AC XY: 40131 AN XY: 158024

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.243 AC: 36828 AN: 151402 Hom.: 6066 Cov.: 30 AF XY: 0.251 AC XY: 18586 AN XY: 73924

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.230

Alfa AF: 0.176 Hom.: 6624

Bravo AF: 0.263

Asia WGS AF: 0.573 AC: 1988 AN: 3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Benign:1

protective, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 13, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.16
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4147611; hg19: chr1-165625023;