chr16-56608579-A-G

Position:

• chr16-56608579-A-G

Variant summary

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

The variant allele was found at a frequency of 0.0592 in 1,581,096 control chromosomes in the GnomAD database, including 3,249 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 0.047 (223 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3026 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

Genes affected

(HGNC:):

MT2A (HGNC:7406): (metallothionein 2A) This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions, altering the intracellular concentration of heavy metals in the cell. These proteins act as anti-oxidants, protect against hydroxyl free radicals, are important in homeostatic control of metal in the cell, and play a role in detoxification of heavy metals. The encoded protein interacts with the protein encoded by the homeobox containing 1 gene in some cell types, controlling intracellular zinc levels, affecting apoptotic and autophagy pathways. Some polymorphisms in this gene are associated with an increased risk of cancer. [provided by RefSeq, Sep 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.56608579A>G		intergenic_region
MT2A	NM_005953.5	c.-77A>G		upstream_gene_variant		ENST00000245185.6	NP_005944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT2A	ENST00000245185.6	c.-77A>G		upstream_gene_variant		1	NM_005953.5	ENSP00000245185.5
MT2A	ENST00000561491.1	c.-77A>G		upstream_gene_variant		2		ENSP00000456804.1
MT2A	ENST00000562017.1	n.-16A>G		upstream_gene_variant		6
MT2A	ENST00000563985.1	n.-5A>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7193 AN: 151726 Hom.: 224 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0411

GnomAD4 exome AF: 0.0605 AC: 86459 AN: 1429256 Hom.: 3026 Cov.: 25 AF XY: 0.0619 AC XY: 44129 AN XY: 713278

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.0910

Gnomad4 ASJ exome AF: 0.0514

Gnomad4 EAS exome AF: 0.0959

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.0564

Gnomad4 OTH exome AF: 0.0606

GnomAD4 genome AF: 0.0474 AC: 7191 AN: 151840 Hom.: 223 Cov.: 32 AF XY: 0.0487 AC XY: 3613 AN XY: 74196

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0589

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0554

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0511 Hom.: 27

Bravo AF: 0.0479

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs28366003; hg19: chr16-56642491; COSMIC: COSV55329893; COSMIC: COSV55329893;