rs8049883

Positions:

• chr16-56639498-G-A
• chr16-56639498-G-C

Variant summary

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

The NM_005946.3(MT1A):​c.94+169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 134,544 control chromosomes in the GnomAD database, including 1,428 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 0.15 (1428 hom., cov: 34)
• Consequence: MT1A NM_005946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1A	NM_005946.3	c.94+169G>A		intron_variant		ENST00000290705.12	NP_005937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1A	ENST00000290705.12	c.94+169G>A		intron_variant		1	NM_005946.3	ENSP00000290705	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 20626 AN: 134432 Hom.: 1424 Cov.: 34

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.153 AC: 20652 AN: 134544 Hom.: 1428 Cov.: 34 AF XY: 0.158 AC XY: 10297 AN XY: 65038

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.166

Alfa AF: 0.126 Hom.: 1101

Bravo AF: 0.135

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.71

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: rs8049883; hg19: chr16-56673410;