dbSNP rs4784708: MT1H:c.28+90G>C (chr16-56670002-G-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_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

5 publications found

Variant links:

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]

MT1H 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=-0.84).

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 rank	MANE	Protein	UniProt
MT1H	NM_005951.2 link	c.28+90G>C		intron_variant	Intron 1 of 2	ENST00000332374.5	NP_005942.1	P80294A0A140VJP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1H	ENST00000332374.5 link	c.28+90G>C		intron_variant	Intron 1 of 2	1	NM_005951.2	ENSP00000330587.5		P80294
MT1H	ENST00000569155.1 link	c.28+90G>C		intron_variant	Intron 1 of 1	1		ENSP00000457114.1		H3BTC4

Frequencies

GnomAD3 genomes

AF:

0.0372

AC:

5662

AN:

152110

Hom.:

138

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.00829

AC:

262

AN:

31598

American (AMR)

AF:

0.0155

AC:

617

AN:

39918

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

347

AN:

25176

East Asian (EAS)

AF:

0.0000762

AC:

AN:

39382

South Asian (SAS)

AF:

0.0228

AC:

1912

AN:

83878

European-Finnish (FIN)

AF:

0.0714

AC:

3801

AN:

53234

Middle Eastern (MID)

AF:

0.0196

AC:

109

AN:

5570

European-Non Finnish (NFE)

AF:

0.0607

AC:

65134

AN:

1072754

Other (OTH)

AF:

0.0422

AC:

2465

AN:

58384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3559

7118

10678

14237

17796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2360

4720

7080

9440

11800

<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:

0.0372

AC:

5662

AN:

152228

Hom.:

138

Cov.:

AF XY:

0.0364

AC XY:

2712

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0107

AC:

444

AN:

41550

American (AMR)

AF:

0.0228

AC:

349

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0205

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0706

AC:

748

AN:

10594

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0573

AC:

3895

AN:

68006

Other (OTH)

AF:

0.0332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

280

561

841

1122

1402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0269

Hom.:

Bravo

AF:

0.0331

Asia WGS

AF:

0.0110

AC:

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

(source)

DANN

Benign

0.44

PhyloP100

-1.5

PromoterAI

-0.055

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over