chr19-6586487-T-C

Position:

• chr19-6586487-T-C

Variant summary

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

The ENST00000245903.4(CD70):​c.197-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,394,454 control chromosomes in the GnomAD database, including 6,766 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 0.094 (712 hom., cov: 30)
  • Exomes 𝑓: 0.097 (6054 hom.)
• Consequence: CD70 ENST00000245903.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD70	NM_001252.5	c.197-82A>G		intron_variant		ENST00000245903.4	NP_001243.1
CD70	NM_001330332.2	c.197-82A>G		intron_variant			NP_001317261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD70	ENST00000245903.4	c.197-82A>G		intron_variant		1	NM_001252.5	ENSP00000245903	P1
CD70	ENST00000423145.7	c.197-82A>G		intron_variant		2		ENSP00000395294

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14217 AN: 151716 Hom.: 714 Cov.: 30

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0971 AC: 120665 AN: 1242620 Hom.: 6054 AF XY: 0.0976 AC XY: 59779 AN XY: 612476

Gnomad4 AFR exome AF: 0.0925

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.0399

Gnomad4 SAS exome AF: 0.0849

Gnomad4 FIN exome AF: 0.0975

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0937 AC: 14229 AN: 151834 Hom.: 712 Cov.: 30 AF XY: 0.0920 AC XY: 6826 AN XY: 74198

Gnomad4 AFR AF: 0.0902

Gnomad4 AMR AF: 0.0751

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0391

Gnomad4 SAS AF: 0.0732

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.103

Alfa AF: 0.101 Hom.: 904

Bravo AF: 0.0916

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.45

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: rs16994592; hg19: chr19-6586498;