rs1006027

Positions:

• chr9-114929033-T-C

Variant summary

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

The NM_001244.4(TNFSF8):​c.195+1076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,056 control chromosomes in the GnomAD database, including 10,241 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 0.36 (10241 hom., cov: 33)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

Genes affected

TNFSF8 (HGNC:11938): (TNF superfamily member 8) 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 TNFRSF8/CD30, which is a cell surface antigen and a marker for Hodgkin lymphoma and related hematologic malignancies. The engagement of this cytokine expressed on B cell surface plays an inhibitory role in modulating Ig class switch. This cytokine was shown to enhance cell proliferation of some lymphoma cell lines, while to induce cell death and reduce cell proliferation of other lymphoma cell lines. The pleiotropic biologic activities of this cytokine on different CD30+ lymphoma cell lines may play a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

DELEC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.195+1076A>G		intron_variant		ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.195+1076A>G		intron_variant			NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.195+1076A>G		intron_variant		1	NM_001244.4	ENSP00000223795.2
TNFSF8	ENST00000618336.4	c.195+1076A>G		intron_variant		3		ENSP00000484651.1
DELEC1	ENST00000648852.1	n.198+7435T>C		intron_variant
DELEC1	ENST00000649565.1	n.226-40551T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54354 AN: 151938 Hom.: 10232 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.358 AC: 54387 AN: 152056 Hom.: 10241 Cov.: 33 AF XY: 0.360 AC XY: 26714 AN XY: 74294

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.360

Alfa AF: 0.375 Hom.: 1372

Bravo AF: 0.355

Asia WGS AF: 0.383 AC: 1327 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.95
DANN	Benign	0.47

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: rs1006027; hg19: chr9-117691313;