chr19-6595768-G-A

Variant names:

• chr19-6595768-G-A
• rs168259
• ENST00000597430.2:c.-213-3193C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

CD70 Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to CD70 deficiency

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000597430.2. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD70	ENST00000597430.2	TSL:3	c.-213-3193C>T		intron	N/A	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

African (AFR) AF: 0.146 AC: 6052 AN: 41492

American (AMR) AF: 0.110 AC: 1683 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3470

East Asian (EAS) AF: 0.0905 AC: 469 AN: 5184

South Asian (SAS) AF: 0.168 AC: 811 AN: 4818

European-Finnish (FIN) AF: 0.0368 AC: 390 AN: 10604

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8803 AN: 68000

Other (OTH) AF: 0.124 AC: 261 AN: 2112

Alfa AF: 0.130 Hom.: 2183

Bravo AF: 0.130

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs168259; hg19: chr19-6595779;