19-6668961-C-T

Variant names:

• chr19-6668961-C-T
• rs1077667
• NM_001376887.1:c.219+890G>A

Variant summary

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

The NM_001376887.1(TNFSF14):​c.219+890G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,130 control chromosomes in the GnomAD database, including 3,252 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 0.19 (3252 hom., cov: 32)
• Consequence: TNFSF14 NM_001376887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.63

Genes affected

TNFSF14 (HGNC:11930): (TNF superfamily member 14) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF14	NM_001376887.1	c.219+890G>A		intron_variant	Intron 1 of 3	ENST00000675206.1	NP_001363816.1
TNFSF14	NM_003807.5	c.219+890G>A		intron_variant	Intron 2 of 4		NP_003798.2
TNFSF14	NM_172014.3	c.111+998G>A		intron_variant	Intron 1 of 3		NP_742011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF14	ENST00000675206.1	c.219+890G>A		intron_variant	Intron 1 of 3		NM_001376887.1	ENSP00000502837.1
TNFSF14	ENST00000599359.1	c.219+890G>A		intron_variant	Intron 2 of 4	1		ENSP00000469049.1
TNFSF14	ENST00000245912.7	c.111+998G>A		intron_variant	Intron 1 of 3	1		ENSP00000245912.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29439 AN: 152012 Hom.: 3249 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.194 AC: 29467 AN: 152130 Hom.: 3252 Cov.: 32 AF XY: 0.201 AC XY: 14913 AN XY: 74336

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.180

Alfa AF: 0.195 Hom.: 6389

Bravo AF: 0.182

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.024
DANN	Benign	0.79

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: rs1077667; hg19: chr19-6668972;