rs168259

Positions:

• chr19-6595768-G-A

Variant summary

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

The ENST00000597430.2(CD70):​c.-213-3193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,178 control chromosomes in the GnomAD database, including 1,309 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 0.13 (1309 hom., cov: 32)
• Consequence: CD70 ENST00000597430.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

Genes affected

CD70 (HGNC:11937): (CD70 molecule) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for TNFRSF27/CD27. It is a surface antigen on activated, but not on resting, T and B lymphocytes. It induces proliferation of costimulated T cells, enhances the generation of cytolytic T cells, and contributes to T cell activation. This cytokine is also reported to play a role in regulating B-cell activation, cytotoxic function of natural killer cells, and immunoglobulin sythesis. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.6595768G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD70	ENST00000597430.2	c.-213-3193C>T		intron_variant		3		ENSP00000470805.2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19103 AN: 152060 Hom.: 1304 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19133 AN: 152178 Hom.: 1309 Cov.: 32 AF XY: 0.122 AC XY: 9073 AN XY: 74412

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0905

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.124

Alfa AF: 0.130 Hom.: 1725

Bravo AF: 0.130

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs168259; hg19: chr19-6595779;