rs3181369

Variant names:

• chr9-114903586-G-A
• rs3181369
• NM_001244.4:c.*345C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-114903586-G-A
• chr9-114903586-G-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.*345C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 542,922 control chromosomes in the GnomAD database, including 41,789 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 (10493 hom., cov: 33)
  • Exomes 𝑓: 0.40 (31296 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 8 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF8	NM_001244.4	MANE Select	c.*345C>T		3_prime_UTR	Exon 4 of 4	NP_001235.1
	TNFSF8	NM_001252290.1		c.409+641C>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.*345C>T		3_prime_UTR	Exon 4 of 4	ENSP00000223795.2
	TNFSF8	ENST00000618336.4	TSL:3	c.409+641C>T		intron	N/A	ENSP00000484651.1
	TNFSF8	ENST00000474301.1	TSL:2	n.82+641C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54998 AN: 151950 Hom.: 10482 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.397 AC: 155234 AN: 390854 Hom.: 31296 Cov.: 6 AF XY: 0.397 AC XY: 73593 AN XY: 185356

African (AFR) AF: 0.232 AC: 1718 AN: 7396

American (AMR) AF: 0.435 AC: 992 AN: 2282

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1317 AN: 3020

East Asian (EAS) AF: 0.267 AC: 816 AN: 3052

South Asian (SAS) AF: 0.402 AC: 3341 AN: 8314

European-Finnish (FIN) AF: 0.372 AC: 356 AN: 956

Middle Eastern (MID) AF: 0.368 AC: 300 AN: 816

European-Non Finnish (NFE) AF: 0.402 AC: 141156 AN: 351400

Other (OTH) AF: 0.385 AC: 5238 AN: 13618

GnomAD4 genome AF: 0.362 AC: 55034 AN: 152068 Hom.: 10493 Cov.: 33 AF XY: 0.365 AC XY: 27133 AN XY: 74324

African (AFR) AF: 0.243 AC: 10095 AN: 41504

American (AMR) AF: 0.453 AC: 6923 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1455 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1344 AN: 5164

South Asian (SAS) AF: 0.402 AC: 1939 AN: 4818

European-Finnish (FIN) AF: 0.407 AC: 4297 AN: 10558

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

European-Non Finnish (NFE) AF: 0.407 AC: 27682 AN: 67970

Other (OTH) AF: 0.362 AC: 763 AN: 2110

Alfa AF: 0.390 Hom.: 29807

Bravo AF: 0.357

Asia WGS AF: 0.395 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.80
PhyloP100		0.66
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: rs3181369; hg19: chr9-117665866;