chr16-56638104-A-C

Variant names:

• chr16-56638104-A-C
• rs56031221
• ENST00000908024.1:c.-227A>C

Variant summary

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

The ENST00000908024.1(MT1A):​c.-227A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,240 control chromosomes in the GnomAD database, including 492 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 0.067 (492 hom., cov: 33)
• Consequence: MT1A ENST00000908024.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 1 publications found

Genes affected

MT1A (HGNC:7393): (metallothionein 1A) 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. The conserved cysteine residues co-ordinate metal ions using mercaptide linkages. 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. Disruption of two metallothionein genes in mouse resulted in defects in protection against heavy metals, oxidative stress, immune reactions, carcinogens, and displayed obesity. [provided by RefSeq, Sep 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908024.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1A	ENST00000908024.1		c.-227A>C		upstream_gene	N/A	ENSP00000578083.1

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10216 AN: 152122 Hom.: 492 Cov.: 33

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.0805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0671 AC: 10212 AN: 152240 Hom.: 492 Cov.: 33 AF XY: 0.0668 AC XY: 4968 AN XY: 74418

African (AFR) AF: 0.0172 AC: 714 AN: 41570

American (AMR) AF: 0.0729 AC: 1115 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.195 AC: 1007 AN: 5164

South Asian (SAS) AF: 0.165 AC: 798 AN: 4822

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10612

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0836 AC: 5684 AN: 67998

Other (OTH) AF: 0.0801 AC: 169 AN: 2110

Alfa AF: 0.0682 Hom.: 58

Bravo AF: 0.0678

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.59
DANN	Benign	0.73
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs56031221; hg19: chr16-56672016;