rs4784708

Positions:

• chr16-56670002-G-C
• chr16-56670002-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.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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT1H	NM_005951.2	c.28+90G>C		intron_variant		ENST00000332374.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT1H	ENST00000332374.5	c.28+90G>C		intron_variant		1	NM_005951.2	P1
MT1H	ENST00000569155.1	c.28+90G>C		intron_variant		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

Gnomad4 AFR exome AF: 0.00829

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.0000762

Gnomad4 SAS exome AF: 0.0228

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0607

Gnomad4 OTH exome AF: 0.0422

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

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.0332

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.44

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: rs4784708; hg19: chr16-56703914;