dbSNP rs7814569: TPD52:n.235+40838T>C (chr8-80177631-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 ENST00000519250.5(TPD52):n.235+40838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,428 control chromosomes in the GnomAD database, including 6,517 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 0.22 ( 6517 hom., cov: 33)

Exomes 𝑓: 0.023 ( 0 hom. )

Consequence

TPD52
ENST00000519250.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Variant links:

Genes affected

TPD52 (HGNC:12005): (tumor protein D52) Enables calcium ion binding activity and protein homodimerization activity. Involved in B cell differentiation. Located in endoplasmic reticulum and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TPD52 links:

LOC105375920 (HGNC:):

LOC105375920 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375920	XR_929095.3 link	n.*23T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52	ENST00000519250.5 link	n.235+40838T>C		intron_variant	Intron 2 of 4	4
TPD52	ENST00000523564.2 link	n.*26T>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33294

AN:

152134

Hom.:

6502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.0556

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.0964

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0811

Gnomad OTH

AF:

0.196

GnomAD4 exome

AF:

0.0227

AC:

AN:

176

Hom.:

Cov.:

AF XY:

0.0319

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0185

AC:

AN:

162

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000005), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.219

AC:

33359

AN:

152252

Hom.:

6517

Cov.:

AF XY:

0.219

AC XY:

16297

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.527

AC:

21895

AN:

41510

American (AMR)

AF:

0.169

AC:

2594

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

462

AN:

3468

East Asian (EAS)

AF:

0.0554

AC:

287

AN:

5182

South Asian (SAS)

AF:

0.221

AC:

1068

AN:

4822

European-Finnish (FIN)

AF:

0.0964

AC:

1024

AN:

10618

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0811

AC:

5517

AN:

68028

Other (OTH)

AF:

0.194

AC:

410

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1082

2164

3245

4327

5409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.118

Hom.:

1160

Bravo

AF:

0.236

Asia WGS

AF:

0.162

AC:

562

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.70

(source)

DANN

Benign

0.46

PhyloP100

-1.7

Splicing

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

Publications

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rs7814569

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over