9-114919590-G-T

Position:

• chr9-114919590-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244.4(TNFSF8):​c.196-1452C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,992 control chromosomes in the GnomAD database, including 10,406 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 (10406 hom., cov: 32)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.196-1452C>A		intron_variant		ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.196-1452C>A		intron_variant			NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.196-1452C>A		intron_variant		1	NM_001244.4	ENSP00000223795	P1
TNFSF8	ENST00000618336.4	c.196-1452C>A		intron_variant		3		ENSP00000484651
DELEC1	ENST00000648852.1	n.50-1860G>T		intron_variant, non_coding_transcript_variant
DELEC1	ENST00000649565.1	n.225+34282G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54745 AN: 151874 Hom.: 10397 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.360 AC: 54779 AN: 151992 Hom.: 10406 Cov.: 32 AF XY: 0.363 AC XY: 26987 AN XY: 74280

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.361

Alfa AF: 0.239 Hom.: 587

Bravo AF: 0.357

Asia WGS AF: 0.380 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs10982450; hg19: chr9-117681870;