chr9-114903099-A-G

Variant names:

• chr9-114903099-A-G
• rs1126711
• NM_001244.4:c.*832T>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.*832T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,096 control chromosomes in the GnomAD database, including 24,930 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 0.55 (24924 hom., cov: 32)
  • Exomes 𝑓: 0.37 (6 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 7 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 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.*832T>C		3_prime_UTR	Exon 4 of 4	NP_001235.1
	TNFSF8	NM_001252290.1		c.409+1128T>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.*832T>C		3_prime_UTR	Exon 4 of 4	ENSP00000223795.2
	TNFSF8	ENST00000872160.1		c.*832T>C		3_prime_UTR	Exon 3 of 3	ENSP00000542219.1
	TNFSF8	ENST00000618336.4	TSL:3	c.409+1128T>C		intron	N/A	ENSP00000484651.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84001 AN: 151922 Hom.: 24882 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.370 AC: 20 AN: 54 Hom.: 6 Cov.: 0 AF XY: 0.192 AC XY: 5 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.295 AC: 13 AN: 44

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.553 AC: 84102 AN: 152042 Hom.: 24924 Cov.: 32 AF XY: 0.555 AC XY: 41280 AN XY: 74312

African (AFR) AF: 0.756 AC: 31384 AN: 41504

American (AMR) AF: 0.643 AC: 9825 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1603 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1747 AN: 5154

South Asian (SAS) AF: 0.437 AC: 2105 AN: 4822

European-Finnish (FIN) AF: 0.493 AC: 5203 AN: 10550

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.450 AC: 30576 AN: 67940

Other (OTH) AF: 0.516 AC: 1088 AN: 2108

Alfa AF: 0.485 Hom.: 8516

Bravo AF: 0.575

Asia WGS AF: 0.484 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.26
PhyloP100		-2.2
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: rs1126711; hg19: chr9-117665379;