rs2742112

Variant names:

• chr12-10172529-C-T
• rs2742112
• NM_001079815.2:c.-95+1678C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM52B	NM_001079815.2	c.-95+1678C>T		intron_variant	Intron 1 of 5		NP_001073283.1
TMEM52B	NM_001384894.1	c.-311+113C>T		intron_variant	Intron 2 of 7		NP_001371823.1
TMEM52B	NM_001384895.1	c.-95+113C>T		intron_variant	Intron 1 of 5		NP_001371824.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56265 AN: 151806 Hom.: 10744 Cov.: 32

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

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.371 AC: 56330 AN: 151922 Hom.: 10765 Cov.: 32 AF XY: 0.375 AC XY: 27805 AN XY: 74244

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.343

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
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2742112; hg19: chr12-10325128;