rs2062545

Positions:

• chr16-56670213-G-A
• chr16-56670213-G-C
• chr16-56670213-G-T

Variant summary

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

The NM_005951.2(MT1H):​c.29-293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,208 control chromosomes in the GnomAD database, including 59,675 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 0.88 (59675 hom., cov: 32)
• Consequence: MT1H NM_005951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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

Verdict is Benign. Variant got -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 = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1H	NM_005951.2	c.29-293G>A		intron_variant		ENST00000332374.5	NP_005942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1H	ENST00000332374.5	c.29-293G>A		intron_variant		1	NM_005951.2	ENSP00000330587.5
MT1H	ENST00000569155.1	c.29-293G>A		intron_variant		1		ENSP00000457114.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133488 AN: 152090 Hom.: 59650 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.877 AC: 133562 AN: 152208 Hom.: 59675 Cov.: 32 AF XY: 0.881 AC XY: 65552 AN XY: 74438

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.928

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.903

Alfa AF: 0.937 Hom.: 72379

Bravo AF: 0.867

Asia WGS AF: 0.949 AC: 3300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2062545; hg19: chr16-56704125;