chr9-114928990-A-G

Position:

• chr9-114928990-A-G

Variant summary

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

The NM_001244.4(TNFSF8):​c.195+1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,158 control chromosomes in the GnomAD database, including 24,512 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 0.54 (24512 hom., cov: 32)
• Consequence: TNFSF8 NM_001244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.195+1119T>C		intron_variant		ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.195+1119T>C		intron_variant			NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.195+1119T>C		intron_variant		1	NM_001244.4	ENSP00000223795	P1
TNFSF8	ENST00000618336.4	c.195+1119T>C		intron_variant		3		ENSP00000484651
DELEC1	ENST00000648852.1	n.198+7392A>G		intron_variant, non_coding_transcript_variant
DELEC1	ENST00000649565.1	n.226-40594A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82321 AN: 152040 Hom.: 24462 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.542 AC: 82439 AN: 152158 Hom.: 24512 Cov.: 32 AF XY: 0.539 AC XY: 40047 AN XY: 74366

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.500

Alfa AF: 0.401 Hom.: 1713

Bravo AF: 0.559

Asia WGS AF: 0.435 AC: 1507 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.86
DANN	Benign	0.38

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: rs1006026; hg19: chr9-117691270;