rs16994592

Variant names:

• chr19-6586487-T-C
• rs16994592
• NM_001252.5:c.197-82A>G

Variant summary

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

The NM_001252.5(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 NM_001252.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 10 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: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD70	NM_001252.5	MANE Select	c.197-82A>G		intron	N/A	NP_001243.1	P32970-1
	CD70	NM_001330332.2		c.197-82A>G		intron	N/A	NP_001317261.1	P32970-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD70	ENST00000245903.4	TSL:1 MANE Select	c.197-82A>G		intron	N/A	ENSP00000245903.2	P32970-1
	CD70	ENST00000423145.7	TSL:2	c.197-82A>G		intron	N/A	ENSP00000395294.2	P32970-2
	CD70	ENST00000894984.1		c.197-82A>G		intron	N/A	ENSP00000565043.1

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

African (AFR) AF: 0.0925 AC: 2620 AN: 28338

American (AMR) AF: 0.0625 AC: 1738 AN: 27806

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2155 AN: 19436

East Asian (EAS) AF: 0.0399 AC: 1497 AN: 37474

South Asian (SAS) AF: 0.0849 AC: 5688 AN: 66966

European-Finnish (FIN) AF: 0.0975 AC: 3528 AN: 36200

Middle Eastern (MID) AF: 0.126 AC: 449 AN: 3566

European-Non Finnish (NFE) AF: 0.101 AC: 97746 AN: 970372

Other (OTH) AF: 0.100 AC: 5244 AN: 52462

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

African (AFR) AF: 0.0902 AC: 3732 AN: 41370

American (AMR) AF: 0.0751 AC: 1145 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3470

East Asian (EAS) AF: 0.0391 AC: 202 AN: 5172

South Asian (SAS) AF: 0.0732 AC: 352 AN: 4812

European-Finnish (FIN) AF: 0.0934 AC: 986 AN: 10552

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7126 AN: 67902

Other (OTH) AF: 0.103 AC: 216 AN: 2098

Alfa AF: 0.0993 Hom.: 1391

Bravo AF: 0.0916

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.45
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16994592; hg19: chr19-6586498;