chr16-56638468-C-G

Variant names:

• chr16-56638468-C-G
• rs9922957
• ENST00000908024.1:c.-47+184C>G

Variant summary

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

The ENST00000908024.1(MT1A):​c.-47+184C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,238 control chromosomes in the GnomAD database, including 1,331 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 (1331 hom., cov: 32)
• Consequence: MT1A ENST00000908024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 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
	MT1A	NM_005946.3	MANE Select	c.-271C>G		upstream_gene	N/A	NP_005937.2	P04731

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1A	ENST00000908024.1		c.-47+184C>G		intron	N/A	ENSP00000578083.1
	MT1A	ENST00000290705.12	TSL:1 MANE Select	c.-271C>G		upstream_gene	N/A	ENSP00000290705.8	P04731
	MT1A	ENST00000927706.1		c.-271C>G		upstream_gene	N/A	ENSP00000597765.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19857 AN: 152120 Hom.: 1327 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.131 AC: 19875 AN: 152238 Hom.: 1331 Cov.: 32 AF XY: 0.133 AC XY: 9924 AN XY: 74440

African (AFR) AF: 0.115 AC: 4786 AN: 41566

American (AMR) AF: 0.141 AC: 2151 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1182 AN: 5148

South Asian (SAS) AF: 0.175 AC: 844 AN: 4826

European-Finnish (FIN) AF: 0.127 AC: 1343 AN: 10616

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

European-Non Finnish (NFE) AF: 0.123 AC: 8374 AN: 68002

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.125 Hom.: 155

Bravo AF: 0.131

Asia WGS AF: 0.196 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		-1.2
PromoterAI		0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9922957; hg19: chr16-56672380;