chr9-114928990-A-G

Variant names:

• chr9-114928990-A-G
• rs1006026
• NM_001244.4:c.195+1119T>C

Variant summary

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

The NM_001244.4(TNFSF8):​c.195+1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,158 control chromosomes in the GnomAD database, including 24,512 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 0.54 (24512 hom., cov: 32)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• Publications: 5 publications found

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:23658): (deleted in esophageal cancer 1) The function of this gene is not known. This gene is located in a region commonly deleted in esophageal squamous cell carcinomas. Gene expression is reduced or absent in these carcinomas and thus this is a candidate tumor suppressor gene for esophageal squamous cell carcinomas. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244.4. 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
	TNFSF8	NM_001244.4	MANE Select	c.195+1119T>C		intron	N/A	NP_001235.1
	TNFSF8	NM_001252290.1		c.195+1119T>C		intron	N/A	NP_001239219.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	ENST00000223795.3	TSL:1 MANE Select	c.195+1119T>C		intron	N/A	ENSP00000223795.2
	TNFSF8	ENST00000872160.1		c.195+1119T>C		intron	N/A	ENSP00000542219.1
	TNFSF8	ENST00000618336.4	TSL:3	c.195+1119T>C		intron	N/A	ENSP00000484651.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82321 AN: 152040 Hom.: 24462 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.542 AC: 82439 AN: 152158 Hom.: 24512 Cov.: 32 AF XY: 0.539 AC XY: 40047 AN XY: 74366

African (AFR) AF: 0.800 AC: 33207 AN: 41508

American (AMR) AF: 0.537 AC: 8214 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1568 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1328 AN: 5182

South Asian (SAS) AF: 0.416 AC: 2008 AN: 4822

European-Finnish (FIN) AF: 0.418 AC: 4419 AN: 10560

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30061 AN: 68000

Other (OTH) AF: 0.500 AC: 1058 AN: 2114

Alfa AF: 0.401 Hom.: 1713

Bravo AF: 0.559

Asia WGS AF: 0.435 AC: 1507 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.86
DANN	Benign	0.38
PhyloP100		-0.98
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: rs1006026; hg19: chr9-117691270;