9-114905862-C-T

Variant names:

• chr9-114905862-C-T
• rs3181195
• NM_001244.4:c.276G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001244.4(TNFSF8):​c.276G>A​(p.Arg92Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,607,498 control chromosomes in the GnomAD database, including 126,273 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 (10459 hom., cov: 31)
  • Exomes 𝑓: 0.40 (115814 hom.)
• Consequence: TNFSF8 NM_001244.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 26 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 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.276G>A	p.Arg92Arg	synonymous	Exon 3 of 4	NP_001235.1	P32971
	TNFSF8	NM_001252290.1		c.276G>A	p.Arg92Arg	synonymous	Exon 3 of 5	NP_001239219.1	A0A087X228

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	ENST00000223795.3	TSL:1 MANE Select	c.276G>A	p.Arg92Arg	synonymous	Exon 3 of 4	ENSP00000223795.2	P32971
	TNFSF8	ENST00000618336.4	TSL:3	c.276G>A	p.Arg92Arg	synonymous	Exon 3 of 5	ENSP00000484651.1	A0A087X228
	TNFSF8	ENST00000872160.1		c.239-1537G>A		intron	N/A	ENSP00000542219.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54891 AN: 151748 Hom.: 10448 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.388 AC: 97254 AN: 250464 AF XY: 0.390

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.396 AC: 576009 AN: 1455632 Hom.: 115814 Cov.: 32 AF XY: 0.396 AC XY: 286980 AN XY: 724452

African (AFR) AF: 0.239 AC: 7954 AN: 33342

American (AMR) AF: 0.443 AC: 19700 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 11496 AN: 26046

East Asian (EAS) AF: 0.310 AC: 12282 AN: 39634

South Asian (SAS) AF: 0.396 AC: 34018 AN: 86000

European-Finnish (FIN) AF: 0.401 AC: 21407 AN: 53384

Middle Eastern (MID) AF: 0.364 AC: 2091 AN: 5748

European-Non Finnish (NFE) AF: 0.401 AC: 443807 AN: 1106818

Other (OTH) AF: 0.386 AC: 23254 AN: 60176

GnomAD4 genome AF: 0.362 AC: 54928 AN: 151866 Hom.: 10459 Cov.: 31 AF XY: 0.365 AC XY: 27065 AN XY: 74198

African (AFR) AF: 0.243 AC: 10072 AN: 41420

American (AMR) AF: 0.452 AC: 6900 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1455 AN: 3462

East Asian (EAS) AF: 0.260 AC: 1337 AN: 5146

South Asian (SAS) AF: 0.402 AC: 1928 AN: 4794

European-Finnish (FIN) AF: 0.407 AC: 4288 AN: 10544

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27650 AN: 67936

Other (OTH) AF: 0.361 AC: 762 AN: 2108

Alfa AF: 0.393 Hom.: 19421

Bravo AF: 0.357

Asia WGS AF: 0.393 AC: 1364 AN: 3478

EpiCase AF: 0.399

EpiControl AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.9
DANN	Benign	0.60
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3181195; hg19: chr9-117668142; COSMIC: COSV56342232; COSMIC: COSV56342232;