rs3181357

Variant names:

• chr9-114930064-G-A
• rs3181357
• NM_001244.4:c.195+45C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-114930064-G-A
• chr9-114930064-G-C
• chr9-114930064-G-T

Variant summary

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

The ENST00000223795.3(TNFSF8):​c.195+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,395,648 control chromosomes in the GnomAD database, including 14,214 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 0.21 (6922 hom., cov: 30)
  • Exomes 𝑓: 0.061 (7292 hom.)
• Consequence: TNFSF8 ENST00000223795.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000223795.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	NM_001244.4	MANE Select	c.195+45C>T		intron	N/A	NP_001235.1
	TNFSF8	NM_001252290.1		c.195+45C>T		intron	N/A	NP_001239219.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	ENST00000223795.3	TSL:1 MANE Select	c.195+45C>T		intron	N/A	ENSP00000223795.2
	DELEC1	ENST00000815338.1		n.392G>A		non_coding_transcript_exon	Exon 3 of 3
	TNFSF8	ENST00000618336.4	TSL:3	c.195+45C>T		intron	N/A	ENSP00000484651.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31251 AN: 151432 Hom.: 6892 Cov.: 30

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.127 AC: 16826 AN: 132704 AF XY: 0.105

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.0349

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.0932

Gnomad NFE exome AF: 0.0478

Gnomad OTH exome AF: 0.0962

GnomAD4 exome AF: 0.0612 AC: 76088 AN: 1244104 Hom.: 7292 Cov.: 25 AF XY: 0.0592 AC XY: 35820 AN XY: 605190

African (AFR) AF: 0.576 AC: 14729 AN: 25564

American (AMR) AF: 0.286 AC: 5580 AN: 19526

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 655 AN: 17396

East Asian (EAS) AF: 0.198 AC: 6237 AN: 31524

South Asian (SAS) AF: 0.0502 AC: 2638 AN: 52568

European-Finnish (FIN) AF: 0.0943 AC: 4435 AN: 47040

Middle Eastern (MID) AF: 0.0675 AC: 331 AN: 4904

European-Non Finnish (NFE) AF: 0.0375 AC: 37288 AN: 995078

Other (OTH) AF: 0.0831 AC: 4195 AN: 50504

GnomAD4 genome AF: 0.207 AC: 31339 AN: 151544 Hom.: 6922 Cov.: 30 AF XY: 0.206 AC XY: 15269 AN XY: 74010

African (AFR) AF: 0.549 AC: 22641 AN: 41230

American (AMR) AF: 0.193 AC: 2933 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3466

East Asian (EAS) AF: 0.149 AC: 769 AN: 5158

South Asian (SAS) AF: 0.0522 AC: 250 AN: 4788

European-Finnish (FIN) AF: 0.0957 AC: 1003 AN: 10486

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0453 AC: 3078 AN: 67898

Other (OTH) AF: 0.167 AC: 350 AN: 2100

Alfa AF: 0.0711 Hom.: 364

Bravo AF: 0.235

Asia WGS AF: 0.126 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		-0.40
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: rs3181357; hg19: chr9-117692344; COSMIC: COSV56342719;