16-56652118-C-G

Position:

• chr16-56652118-C-G

Variant summary

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

The NM_005947.3(MT1B):​c.28+137C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,056,732 control chromosomes in the GnomAD database, including 397,287 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 0.80 (50256 hom., cov: 34)
  • Exomes 𝑓: 0.87 (347031 hom.)
• Consequence: MT1B NM_005947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

MT1B (HGNC:7394): (metallothionein 1B) The protein encoded by this gene binds heavy metals and protects against toxicity from heavy metal ions. This gene is found in a cluster of similar genes on chromosome 16. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT1B	NM_005947.3	c.28+137C>G		intron_variant		ENST00000334346.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT1B	ENST00000334346.3	c.28+137C>G		intron_variant		1	NM_005947.3	P1
MT1B	ENST00000562399.1	c.28+137C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121882 AN: 152102 Hom.: 50237 Cov.: 34

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.810

GnomAD4 exome AF: 0.873 AC: 789944 AN: 904512 Hom.: 347031 AF XY: 0.872 AC XY: 404168 AN XY: 463586

Gnomad4 AFR exome AF: 0.592

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.774

Gnomad4 SAS exome AF: 0.807

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.895

Gnomad4 OTH exome AF: 0.850

GnomAD4 genome AF: 0.801 AC: 121943 AN: 152220 Hom.: 50256 Cov.: 34 AF XY: 0.805 AC XY: 59926 AN XY: 74436

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.894

Gnomad4 OTH AF: 0.810

Alfa AF: 0.851 Hom.: 6649

Bravo AF: 0.786

Asia WGS AF: 0.775 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs964372; hg19: chr16-56686030;