chr19-6585024-C-A

Variant names:

• chr19-6585024-C-A
• rs2059154
• NM_001330332.2:c.448+1130G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330332.2(CD70):​c.448+1130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,692 control chromosomes in the GnomAD database, including 11,365 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 0.38 (11365 hom., cov: 31)
• Consequence: CD70 NM_001330332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD70	NM_001330332.2	c.448+1130G>T		intron_variant	Intron 3 of 3		NP_001317261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD70	ENST00000423145.7	c.448+1130G>T		intron_variant	Intron 3 of 3	2		ENSP00000395294.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57979 AN: 151574 Hom.: 11357 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.382 AC: 58006 AN: 151692 Hom.: 11365 Cov.: 31 AF XY: 0.386 AC XY: 28580 AN XY: 74088

African (AFR) AF: 0.334 AC: 13799 AN: 41346

American (AMR) AF: 0.326 AC: 4961 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1223 AN: 3460

East Asian (EAS) AF: 0.679 AC: 3499 AN: 5152

South Asian (SAS) AF: 0.426 AC: 2053 AN: 4816

European-Finnish (FIN) AF: 0.441 AC: 4627 AN: 10494

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26528 AN: 67906

Other (OTH) AF: 0.406 AC: 852 AN: 2096

Alfa AF: 0.375 Hom.: 1302

Bravo AF: 0.377

Asia WGS AF: 0.534 AC: 1856 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	0.89
DANN	Benign	0.36
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2059154; hg19: chr19-6585035;