rs7190725

Variant names:

• chr16-56639378-G-T
• rs7190725
• NM_005946.3:c.94+49G>T

Variant summary

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

The NM_005946.3(MT1A):​c.94+49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,586,494 control chromosomes in the GnomAD database, including 14,187 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 0.13 (1341 hom., cov: 34)
  • Exomes 𝑓: 0.13 (12846 hom.)
• Consequence: MT1A NM_005946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1A	NM_005946.3	c.94+49G>T		intron_variant	Intron 2 of 2	ENST00000290705.12	NP_005937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1A	ENST00000290705.12	c.94+49G>T		intron_variant	Intron 2 of 2	1	NM_005946.3	ENSP00000290705.8

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19838 AN: 152114 Hom.: 1337 Cov.: 34

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.144 AC: 36013 AN: 250018 AF XY: 0.144

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.132 AC: 188951 AN: 1434262 Hom.: 12846 Cov.: 32 AF XY: 0.132 AC XY: 94673 AN XY: 714932

African (AFR) AF: 0.112 AC: 3735 AN: 33248

American (AMR) AF: 0.159 AC: 7051 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 4985 AN: 25754

East Asian (EAS) AF: 0.218 AC: 8591 AN: 39480

South Asian (SAS) AF: 0.163 AC: 14017 AN: 85802

European-Finnish (FIN) AF: 0.120 AC: 6309 AN: 52364

Middle Eastern (MID) AF: 0.120 AC: 678 AN: 5672

European-Non Finnish (NFE) AF: 0.124 AC: 134985 AN: 1088184

Other (OTH) AF: 0.145 AC: 8600 AN: 59298

GnomAD4 genome AF: 0.130 AC: 19855 AN: 152232 Hom.: 1341 Cov.: 34 AF XY: 0.133 AC XY: 9920 AN XY: 74426

African (AFR) AF: 0.115 AC: 4786 AN: 41548

American (AMR) AF: 0.138 AC: 2108 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1200 AN: 5170

South Asian (SAS) AF: 0.177 AC: 853 AN: 4828

European-Finnish (FIN) AF: 0.127 AC: 1343 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8369 AN: 67998

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.127 Hom.: 3502

Bravo AF: 0.130

Asia WGS AF: 0.199 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.86
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7190725; hg19: chr16-56673290; COSMIC: COSV51947984; COSMIC: COSV51947984;