chr8-80177631-A-G

Variant names:

• chr8-80177631-A-G
• rs7814569
• ENST00000519250.5:n.235+40838T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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]

LOC105375920 (HGNC:):

ACMG classification

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	n.*23T>C		downstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33294 AN: 152134 Hom.: 6502 Cov.: 33

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: 4 AN: 176 Hom.: 0 Cov.: 0 AF XY: 0.0319 AC XY: 3 AN XY: 94

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0185 AC: 3 AN: 162

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ 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.

GnomAD4 genome AF: 0.219 AC: 33359 AN: 152252 Hom.: 6517 Cov.: 33 AF XY: 0.219 AC XY: 16297 AN XY: 74440

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: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5517 AN: 68028

Other (OTH) AF: 0.194 AC: 410 AN: 2114

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
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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Other links and lift over

dbSNP: rs7814569; hg19: chr8-81089866;