Genetic Variant NM_005947.3:c.95-68T>C (chr16-56652906-T-C) – 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.95-68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,542,142 control chromosomes in the GnomAD database, including 197,693 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 0.46 ( 16687 hom., cov: 33)

Exomes 𝑓: 0.51 ( 181006 hom. )

Consequence

MT1B
NM_005947.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

17 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:

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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 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.95-68T>C		intron	N/A	NP_005938.1	P07438

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1B	ENST00000334346.3	TSL:1 MANE Select	c.95-68T>C		intron	N/A	ENSP00000334998.2	P07438
	MT1B	ENST00000562399.1	TSL:3	c.93-68T>C		intron	N/A	ENSP00000456056.1	H3BR34

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70083

AN:

151936

Hom.:

16679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.794

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.507

AC:

704499

AN:

1390088

Hom.:

181006

AF XY:

0.509

AC XY:

353792

AN XY:

695752

show subpopulations

African (AFR)

AF:

0.340

AC:

10860

AN:

31930

American (AMR)

AF:

0.404

AC:

18014

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

12946

AN:

25618

East Asian (EAS)

AF:

0.308

AC:

12119

AN:

39300

South Asian (SAS)

AF:

0.518

AC:

43803

AN:

84574

European-Finnish (FIN)

AF:

0.509

AC:

27020

AN:

53100

Middle Eastern (MID)

AF:

0.513

AC:

2175

AN:

4236

European-Non Finnish (NFE)

AF:

0.523

AC:

548959

AN:

1048934

Other (OTH)

AF:

0.495

AC:

28603

AN:

57806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

18008

36016

54023

72031

90039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15188

30376

45564

60752

75940

<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:

0.461

AC:

70122

AN:

152054

Hom.:

16687

Cov.:

AF XY:

0.462

AC XY:

34333

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.347

AC:

14387

AN:

41460

American (AMR)

AF:

0.446

AC:

6815

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

1741

AN:

3468

East Asian (EAS)

AF:

0.323

AC:

1669

AN:

5174

South Asian (SAS)

AF:

0.514

AC:

2478

AN:

4822

European-Finnish (FIN)

AF:

0.515

AC:

5450

AN:

10574

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.526

AC:

35732

AN:

67956

Other (OTH)

AF:

0.473

AC:

999

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1938

3876

5815

7753

9691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<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:

0.469

Hom.:

2545

Bravo

AF:

0.448

Asia WGS

AF:

0.411

AC:

1427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.5

(source)

DANN

Benign

0.59

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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