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
• Publications: 2 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000519250.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52	ENST00000519250.5	TSL:4	n.235+40838T>C		intron	N/A
	TPD52	ENST00000523564.2	TSL:5	n.*26T>C		downstream_gene	N/A

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 = 0.00000477346), 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 v4.9

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

Other links and lift over

dbSNP: rs7814569; hg19: chr8-81089866;