chr16-56670002-G-C

Variant names:

• chr16-56670002-G-C
• rs4784708
• NM_005951.2:c.28+90G>C

Variant summary

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

The NM_005951.2(MT1H):​c.28+90G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,562,122 control chromosomes in the GnomAD database, including 2,399 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 0.037 (138 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2261 hom.)
• Consequence: MT1H NM_005951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 5 publications found

Genes affected

MT1H (HGNC:7400): (metallothionein 1H) Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion and cellular response to zinc ion. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005951.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1H	NM_005951.2	MANE Select	c.28+90G>C		intron	N/A	NP_005942.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1H	ENST00000332374.5	TSL:1 MANE Select	c.28+90G>C		intron	N/A	ENSP00000330587.5
	MT1H	ENST00000569155.1	TSL:1	c.28+90G>C		intron	N/A	ENSP00000457114.1

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5662 AN: 152110 Hom.: 138 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0336

GnomAD4 exome AF: 0.0529 AC: 74650 AN: 1409894 Hom.: 2261 AF XY: 0.0521 AC XY: 36658 AN XY: 703806

African (AFR) AF: 0.00829 AC: 262 AN: 31598

American (AMR) AF: 0.0155 AC: 617 AN: 39918

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 347 AN: 25176

East Asian (EAS) AF: 0.0000762 AC: 3 AN: 39382

South Asian (SAS) AF: 0.0228 AC: 1912 AN: 83878

European-Finnish (FIN) AF: 0.0714 AC: 3801 AN: 53234

Middle Eastern (MID) AF: 0.0196 AC: 109 AN: 5570

European-Non Finnish (NFE) AF: 0.0607 AC: 65134 AN: 1072754

Other (OTH) AF: 0.0422 AC: 2465 AN: 58384

GnomAD4 genome AF: 0.0372 AC: 5662 AN: 152228 Hom.: 138 Cov.: 33 AF XY: 0.0364 AC XY: 2712 AN XY: 74434

African (AFR) AF: 0.0107 AC: 444 AN: 41550

American (AMR) AF: 0.0228 AC: 349 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4818

European-Finnish (FIN) AF: 0.0706 AC: 748 AN: 10594

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0573 AC: 3895 AN: 68006

Other (OTH) AF: 0.0332 AC: 70 AN: 2108

Alfa AF: 0.0269 Hom.: 14

Bravo AF: 0.0331

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.44
PhyloP100		-1.5
PromoterAI		-0.055	Neutral
Mutation Taster		=100/0	polymorphism

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: rs4784708; hg19: chr16-56703914;