dbSNP rs1610216: LOC124903695:n.62T>C (chr16-56608372-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XR_007065079.1(LOC124903695):n.62T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 419,088 control chromosomes in the GnomAD database, including 17,851 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 0.30 ( 8985 hom., cov: 33)

Exomes 𝑓: 0.23 ( 8866 hom. )

Consequence

LOC124903695
XR_007065079.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.693

Publications

26 publications found

Variant links:

Genes affected

LOC124903695 (HGNC:):

LOC124903695 links:

MT2A (HGNC:7406): (metallothionein 2A) This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions, altering the intracellular concentration of heavy metals in the cell. These proteins act as anti-oxidants, protect against hydroxyl free radicals, are important in homeostatic control of metal in the cell, and play a role in detoxification of heavy metals. The encoded protein interacts with the protein encoded by the homeobox containing 1 gene in some cell types, controlling intracellular zinc levels, affecting apoptotic and autophagy pathways. Some polymorphisms in this gene are associated with an increased risk of cancer. [provided by RefSeq, Sep 2017]

MT2A 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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903695	XR_007065079.1 link	n.62T>C		non_coding_transcript_exon_variant	Exon 1 of 2
MT2A	NM_005953.5 link	c.-284A>G		upstream_gene_variant		ENST00000245185.6	NP_005944.1	P02795

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MT2A	ENST00000245185.6 link	c.-284A>G	upstream_gene_variant	1	NM_005953.5	ENSP00000245185.5	P02795
MT2A	ENST00000561491.1 link	c.-284A>G	upstream_gene_variant	2		ENSP00000456804.1	H3BSP9
MT2A	ENST00000562017.1 link	n.-223A>G	upstream_gene_variant	6
MT2A	ENST00000563985.1 link	n.-212A>G	upstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46086

AN:

151986

Hom.:

8959

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.228

AC:

60958

AN:

266984

Hom.:

8866

Cov.:

AF XY:

0.233

AC XY:

32733

AN XY:

140360

show subpopulations

African (AFR)

AF:

0.510

AC:

2602

AN:

5104

American (AMR)

AF:

0.236

AC:

1539

AN:

6534

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

1376

AN:

7920

East Asian (EAS)

AF:

0.552

AC:

9224

AN:

16698

South Asian (SAS)

AF:

0.347

AC:

8333

AN:

23988

European-Finnish (FIN)

AF:

0.140

AC:

3080

AN:

21978

Middle Eastern (MID)

AF:

0.209

AC:

255

AN:

1220

European-Non Finnish (NFE)

AF:

0.184

AC:

30825

AN:

167616

Other (OTH)

AF:

0.234

AC:

3724

AN:

15926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2057

4114

6170

8227

10284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.303

AC:

46149

AN:

152104

Hom.:

8985

Cov.:

AF XY:

0.304

AC XY:

22610

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.523

AC:

21673

AN:

41478

American (AMR)

AF:

0.246

AC:

3767

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

600

AN:

3472

East Asian (EAS)

AF:

0.622

AC:

3205

AN:

5152

South Asian (SAS)

AF:

0.365

AC:

1759

AN:

4822

European-Finnish (FIN)

AF:

0.141

AC:

1495

AN:

10602

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.188

AC:

12809

AN:

67964

Other (OTH)

AF:

0.262

AC:

553

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1518

3037

4555

6074

7592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.245

Hom.:

1534

Bravo

AF:

0.324

Asia WGS

AF:

0.476

AC:

1654

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.0

(source)

DANN

Benign

0.56

PhyloP100

-0.69

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over