rs2062546

Positions:

• chr16-56670305-T-A
• chr16-56670305-T-C

Variant summary

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

The ENST00000332374.5(MT1H):​c.29-201T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,060 control chromosomes in the GnomAD database, including 650 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 0.069 (650 hom., cov: 33)
• Consequence: MT1H ENST00000332374.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1H	NM_005951.2	c.29-201T>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.29-201T>A		intron_variant		1	NM_005951.2	ENSP00000330587	P1
MT1H	ENST00000569155.1	c.29-201T>A		intron_variant		1		ENSP00000457114

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10452 AN: 151942 Hom.: 647 Cov.: 33

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0688 AC: 10459 AN: 152060 Hom.: 650 Cov.: 33 AF XY: 0.0726 AC XY: 5396 AN XY: 74366

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0855

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0257 Hom.: 17

Bravo AF: 0.0767

Asia WGS AF: 0.168 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.69

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: rs2062546; hg19: chr16-56704217; COSMIC: COSV60090838; COSMIC: COSV60090838;