12-16514230-C-A

Position:

• chr12-16514230-C-A

Variant summary

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

The XM_047428857.1(MGST1):​c.*17-75298C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 304,996 control chromosomes in the GnomAD database, including 236 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 0.0087 (56 hom., cov: 33)
  • Exomes 𝑓: 0.022 (180 hom.)
• Consequence: MGST1 XM_047428857.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

Genes affected

MGST1 (HGNC:7061): (microsomal glutathione S-transferase 1) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, two of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. Other family members, demonstrating glutathione S-transferase and peroxidase activities, are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. This gene encodes a protein that catalyzes the conjugation of glutathione to electrophiles and the reduction of lipid hydroperoxides. This protein is localized to the endoplasmic reticulum and outer mitochondrial membrane where it is thought to protect these membranes from oxidative stress. Several transcript variants, some non-protein coding and some protein coding, have been found for this gene. [provided by RefSeq, May 2012]

ENSG00000256450 (HGNC:):

GOT2P4 (HGNC:22936):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST1	XM_047428857.1	c.*17-75298C>A		intron_variant			XP_047284813.1
GOT2P4		n.16514230C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000256450	ENST00000540992.1	n.786C>A		non_coding_transcript_exon_variant	1/1	6
MGST1	ENST00000538857.1	n.483-75298C>A		intron_variant		3
MGST1	ENST00000539036.5	n.401-94864C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00875 AC: 1332 AN: 152156 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.0222 AC: 3391 AN: 152722 Hom.: 180 Cov.: 0 AF XY: 0.0288 AC XY: 2431 AN XY: 84518

Gnomad4 AFR exome AF: 0.000495

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.000900

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.0790

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000405

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.00873 AC: 1329 AN: 152274 Hom.: 56 Cov.: 33 AF XY: 0.0109 AC XY: 809 AN XY: 74460

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00158 Hom.: 2

Bravo AF: 0.00793

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.15
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11056970; hg19: chr12-16667164;