chr9-114903155-A-G

Variant names:

• chr9-114903155-A-G
• rs3181372
• NM_001244.4:c.*776T>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.*776T>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 0.572 in 152,188 control chromosomes in the GnomAD database, including 26,798 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 0.57 (26786 hom., cov: 33)
  • Exomes 𝑓: 0.61 (12 hom.)
• Consequence: TNFSF8 NM_001244.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 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.*776T>C		3_prime_UTR	Exon 4 of 4	NP_001235.1
	TNFSF8	NM_001252290.1		c.409+1072T>C		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.*776T>C		3_prime_UTR	Exon 4 of 4	ENSP00000223795.2
	TNFSF8	ENST00000618336.4	TSL:3	c.409+1072T>C		intron	N/A	ENSP00000484651.1
	TNFSF8	ENST00000474301.1	TSL:2	n.82+1072T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86840 AN: 152004 Hom.: 26730 Cov.: 33

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.609 AC: 39 AN: 64 Hom.: 12 Cov.: 0 AF XY: 0.595 AC XY: 25 AN XY: 42

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.596 AC: 31 AN: 52

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

GnomAD4 genome AF: 0.572 AC: 86964 AN: 152124 Hom.: 26786 Cov.: 33 AF XY: 0.574 AC XY: 42699 AN XY: 74358

African (AFR) AF: 0.800 AC: 33204 AN: 41528

American (AMR) AF: 0.648 AC: 9902 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2098 AN: 5172

South Asian (SAS) AF: 0.453 AC: 2186 AN: 4826

European-Finnish (FIN) AF: 0.504 AC: 5340 AN: 10588

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30809 AN: 67940

Other (OTH) AF: 0.529 AC: 1115 AN: 2108

Alfa AF: 0.501 Hom.: 56567

Bravo AF: 0.595

Asia WGS AF: 0.519 AC: 1798 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	0.24
DANN	Benign	0.20
PhyloP100		-2.3
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: rs3181372; hg19: chr9-117665435;