Genetic Variant MT1B:c.28+137C>G (chr16-56652118-C-G) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

18 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:

Genome browser will be placed here

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=-1.01).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005947.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1B	NM_005947.3	MANE Select	c.28+137C>G		intron	N/A	NP_005938.1	P07438

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MT1B	ENST00000334346.3	TSL:1 MANE Select	c.28+137C>G	intron	N/A	ENSP00000334998.2	P07438
MT1B	ENST00000562399.1	TSL:3	c.28+137C>G	intron	N/A	ENSP00000456056.1	H3BR34
ENSG00000259923	ENST00000568608.1	TSL:5	n.178+137C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121882

AN:

152102

Hom.:

50237

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.592

AC:

13077

AN:

22082

American (AMR)

AF:

0.879

AC:

31146

AN:

35452

Ashkenazi Jewish (ASJ)

AF:

0.788

AC:

16205

AN:

20570

East Asian (EAS)

AF:

0.774

AC:

26983

AN:

34884

South Asian (SAS)

AF:

0.807

AC:

55318

AN:

68508

European-Finnish (FIN)

AF:

0.946

AC:

38174

AN:

40364

Middle Eastern (MID)

AF:

0.842

AC:

3882

AN:

4610

European-Non Finnish (NFE)

AF:

0.895

AC:

569528

AN:

636110

Other (OTH)

AF:

0.850

AC:

35631

AN:

41932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4878

9755

14633

19510

24388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9522

19044

28566

38088

47610

<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:

0.801

AC:

121943

AN:

152220

Hom.:

50256

Cov.:

AF XY:

0.805

AC XY:

59926

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.598

AC:

24813

AN:

41516

American (AMR)

AF:

0.856

AC:

13090

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

2731

AN:

3472

East Asian (EAS)

AF:

0.719

AC:

3707

AN:

5158

South Asian (SAS)

AF:

0.801

AC:

3869

AN:

4828

European-Finnish (FIN)

AF:

0.954

AC:

10134

AN:

10624

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.894

AC:

60783

AN:

68010

Other (OTH)

AF:

0.810

AC:

1713

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1120

2241

3361

4482

5602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.851

Hom.:

6649

Bravo

AF:

0.786

Asia WGS

AF:

0.775

AC:

2693

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.57

(source)

DANN

Benign

0.57

PhyloP100

-1.7

PromoterAI

-0.028

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over