rs1610216

Variant names:

• chr16-56608372-A-G
• rs1610216
• XR_007065079.1:n.62T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-56608372-A-G
• chr16-56608372-A-T

Variant summary

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

The XR_007065079.1(LOC124903695):​n.62T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 419,088 control chromosomes in the GnomAD database, including 17,851 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 0.30 (8985 hom., cov: 33)
  • Exomes 𝑓: 0.23 (8866 hom.)
• Consequence: LOC124903695 XR_007065079.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693
• Publications: 26 publications found

Genes affected

LOC124903695 (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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000245185.6. 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
	MT2A	NM_005953.5	MANE Select	c.-284A>G		upstream_gene	N/A	NP_005944.1	P02795

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT2A	ENST00000245185.6	TSL:1 MANE Select	c.-284A>G		upstream_gene	N/A	ENSP00000245185.5	P02795
	MT2A	ENST00000561491.1	TSL:2	c.-284A>G		upstream_gene	N/A	ENSP00000456804.1	H3BSP9
	MT2A	ENST00000931885.1		c.-284A>G		upstream_gene	N/A	ENSP00000601944.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46086 AN: 151986 Hom.: 8959 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.228 AC: 60958 AN: 266984 Hom.: 8866 Cov.: 2 AF XY: 0.233 AC XY: 32733 AN XY: 140360

African (AFR) AF: 0.510 AC: 2602 AN: 5104

American (AMR) AF: 0.236 AC: 1539 AN: 6534

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 1376 AN: 7920

East Asian (EAS) AF: 0.552 AC: 9224 AN: 16698

South Asian (SAS) AF: 0.347 AC: 8333 AN: 23988

European-Finnish (FIN) AF: 0.140 AC: 3080 AN: 21978

Middle Eastern (MID) AF: 0.209 AC: 255 AN: 1220

European-Non Finnish (NFE) AF: 0.184 AC: 30825 AN: 167616

Other (OTH) AF: 0.234 AC: 3724 AN: 15926

GnomAD4 genome AF: 0.303 AC: 46149 AN: 152104 Hom.: 8985 Cov.: 33 AF XY: 0.304 AC XY: 22610 AN XY: 74384

African (AFR) AF: 0.523 AC: 21673 AN: 41478

American (AMR) AF: 0.246 AC: 3767 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3472

East Asian (EAS) AF: 0.622 AC: 3205 AN: 5152

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4822

European-Finnish (FIN) AF: 0.141 AC: 1495 AN: 10602

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12809 AN: 67964

Other (OTH) AF: 0.262 AC: 553 AN: 2108

Alfa AF: 0.245 Hom.: 1534

Bravo AF: 0.324

Asia WGS AF: 0.476 AC: 1654 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.0
DANN	Benign	0.56
PhyloP100		-0.69
PromoterAI		0.013	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1610216; hg19: chr16-56642284;