rs1862511

chr19-6586257-G-Achr19-6586257-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001252.5(CD70):c.345C>T(p.Cys115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,640 control chromosomes in the GnomAD database, including 77,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6608 hom., cov: 31)
  • Exomes 𝑓: 0.30 (71098 hom.)
• Consequence: CD70 NM_001252.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 19-6586257-G-A is Benign according to our data. Variant chr19-6586257-G-A is described in ClinVar as [Benign]. Clinvar id is 2628186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD70	NM_001252.5	c.345C>T	p.Cys115=	synonymous_variant	3/3	ENST00000245903.4
CD70	NM_001330332.2	c.345C>T	p.Cys115=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD70	ENST00000245903.4	c.345C>T	p.Cys115=	synonymous_variant	3/3	1	NM_001252.5	P1
CD70	ENST00000423145.7	c.345C>T	p.Cys115=	synonymous_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42669 AN: 151908 Hom.: 6611 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.294

GnomAD3 exomes AF: 0.319 AC: 80052 AN: 251254 Hom.: 14777 AF XY: 0.323 AC XY: 43855 AN XY: 135814

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.695

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.302 AC: 441946 AN: 1461614 Hom.: 71098 Cov.: 38 AF XY: 0.304 AC XY: 220865 AN XY: 727126

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.281 AC: 42672 AN: 152026 Hom.: 6608 Cov.: 31 AF XY: 0.288 AC XY: 21377 AN XY: 74292

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.296

Alfa AF: 0.287 Hom.: 12846

Bravo AF: 0.272

Asia WGS AF: 0.477 AC: 1656 AN: 3478

EpiCase AF: 0.293

EpiControl AF: 0.298

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	7.0
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1862511; hg19: chr19-6586268; COSMIC: COSV55566324; COSMIC: COSV55566324;