Genetic Variant MT1B:c.29-13C>T (chr16-56652558-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005947.3(MT1B):c.29-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,611,938 control chromosomes in the GnomAD database, including 167,173 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 0.41 ( 13396 hom., cov: 33)

Exomes 𝑓: 0.46 ( 153777 hom. )

Consequence

MT1B
NM_005947.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.603

Publications

15 publications found

Variant links:

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]

MT1B links:

ENSG00000259923 (HGNC:):

ENSG00000259923 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1B	NM_005947.3 link	c.29-13C>T		intron_variant	Intron 1 of 2	ENST00000334346.3	NP_005938.1	P07438

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MT1B	ENST00000334346.3 link	c.29-13C>T	intron_variant	Intron 1 of 2	1	NM_005947.3	ENSP00000334998.2	P07438
MT1B	ENST00000562399.1 link	c.29-13C>T	intron_variant	Intron 1 of 2	3		ENSP00000456056.1	H3BR34
ENSG00000259923	ENST00000568608.1 link	n.179-13C>T	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62634

AN:

151978

Hom.:

13386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.418

GnomAD2 exomes

AF:

0.459

AC:

115312

AN:

251350

AF XY:

0.458

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.531

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.467

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.456

AC:

665648

AN:

1459842

Hom.:

153777

Cov.:

AF XY:

0.456

AC XY:

331083

AN XY:

726250

show subpopulations

African (AFR)

AF:

0.275

AC:

9188

AN:

33436

American (AMR)

AF:

0.530

AC:

23666

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

10423

AN:

26078

East Asian (EAS)

AF:

0.604

AC:

23914

AN:

39618

South Asian (SAS)

AF:

0.453

AC:

39067

AN:

86226

European-Finnish (FIN)

AF:

0.468

AC:

24941

AN:

53258

Middle Eastern (MID)

AF:

0.468

AC:

2695

AN:

5764

European-Non Finnish (NFE)

AF:

0.455

AC:

504879

AN:

1110502

Other (OTH)

AF:

0.446

AC:

26875

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

17268

34535

51803

69070

86338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15222

30444

45666

60888

76110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.412

AC:

62654

AN:

152096

Hom.:

13396

Cov.:

AF XY:

0.415

AC XY:

30865

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.286

AC:

11859

AN:

41524

American (AMR)

AF:

0.486

AC:

7425

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1418

AN:

3470

East Asian (EAS)

AF:

0.567

AC:

2926

AN:

5158

South Asian (SAS)

AF:

0.452

AC:

2181

AN:

4828

European-Finnish (FIN)

AF:

0.465

AC:

4921

AN:

10574

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.452

AC:

30705

AN:

67940

Other (OTH)

AF:

0.419

AC:

885

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1883

3766

5649

7532

9415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.367

Hom.:

2050

Bravo

AF:

0.410

Asia WGS

AF:

0.503

AC:

1752

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.8

(source)

DANN

Benign

0.68

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over