Genetic Variant NM_001079815.2:c.-95+1678C>T (chr12-10172529-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_001079815.2(TMEM52B):c.-95+1678C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 155,756 control chromosomes in the GnomAD database, including 10,994 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 0.37 ( 10765 hom., cov: 32)

Exomes 𝑓: 0.33 ( 229 hom. )

Consequence

TMEM52B
NM_001079815.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.400

Publications

3 publications found

Variant links:

Genes affected

TMEM52B (HGNC:26438): (transmembrane protein 52B) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM52B links:

OLR1 (HGNC:8133): (oxidized low density lipoprotein receptor 1) This gene encodes a low density lipoprotein receptor that belongs to the C-type lectin superfamily. This gene is regulated through the cyclic AMP signaling pathway. The encoded protein binds, internalizes and degrades oxidized low-density lipoprotein. This protein may be involved in the regulation of Fas-induced apoptosis. This protein may play a role as a scavenger receptor. Mutations of this gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

OLR1 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TMEM52B	NM_001079815.2 link	c.-95+1678C>T	intron_variant	Intron 1 of 5	NP_001073283.1	Q4KMG9-1
TMEM52B	NM_001384894.1 link	c.-311+113C>T	intron_variant	Intron 2 of 7	NP_001371823.1
TMEM52B	NM_001384895.1 link	c.-95+113C>T	intron_variant	Intron 1 of 5	NP_001371824.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TMEM52B	ENST00000381923.6 link	c.-95+1678C>T	intron_variant	Intron 1 of 5	5	ENSP00000371348.2	Q4KMG9-1
TMEM52B	ENST00000545924.1 link	n.123+1678C>T	intron_variant	Intron 1 of 1	3
TMEM52B	ENST00000334148.7 link	n.*111C>T	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56265

AN:

151806

Hom.:

10744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.563

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.337

GnomAD4 exome

AF:

0.327

AC:

1255

AN:

3834

Hom.:

229

AF XY:

0.326

AC XY:

656

AN XY:

2010

show subpopulations

African (AFR)

AF:

0.262

AC:

AN:

American (AMR)

AF:

0.336

AC:

254

AN:

756

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

AN:

East Asian (EAS)

AF:

0.528

AC:

AN:

178

South Asian (SAS)

AF:

0.381

AC:

160

AN:

420

European-Finnish (FIN)

AF:

0.279

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.301

AC:

639

AN:

2120

Other (OTH)

AF:

0.350

AC:

AN:

160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.371

AC:

56330

AN:

151922

Hom.:

10765

Cov.:

AF XY:

0.375

AC XY:

27805

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.448

AC:

18545

AN:

41386

American (AMR)

AF:

0.349

AC:

5323

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

955

AN:

3468

East Asian (EAS)

AF:

0.562

AC:

2912

AN:

5180

South Asian (SAS)

AF:

0.435

AC:

2098

AN:

4824

European-Finnish (FIN)

AF:

0.361

AC:

3800

AN:

10532

Middle Eastern (MID)

AF:

0.233

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.317

AC:

21512

AN:

67946

Other (OTH)

AF:

0.343

AC:

725

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1811

3622

5433

7244

9055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.354

Hom.:

1422

Bravo

AF:

0.372

Asia WGS

AF:

0.500

AC:

1735

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.9

(source)

DANN

Benign

0.45

PhyloP100

-0.40

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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