Genetic Variant TNFSF14:c.219+890G>A (chr19-6668961-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.63

Publications

94 publications found

Variant links:

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]

TNFSF14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
TNFSF14	NM_001376887.1 link	c.219+890G>A	intron_variant	Intron 1 of 3	ENST00000675206.1	NP_001363816.1
TNFSF14	NM_003807.5 link	c.219+890G>A	intron_variant	Intron 2 of 4		NP_003798.2
TNFSF14	NM_172014.3 link	c.111+998G>A	intron_variant	Intron 1 of 3		NP_742011.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TNFSF14	ENST00000675206.1 link	c.219+890G>A	intron_variant	Intron 1 of 3		NM_001376887.1	ENSP00000502837.1
TNFSF14	ENST00000599359.1 link	c.219+890G>A	intron_variant	Intron 2 of 4	1		ENSP00000469049.1
TNFSF14	ENST00000245912.7 link	c.111+998G>A	intron_variant	Intron 1 of 3	1		ENSP00000245912.3
TNFSF14	ENST00000850589.1 link	n.219+890G>A	intron_variant	Intron 1 of 4			ENSP00000520876.1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29439

AN:

152012

Hom.:

3249

Cov.:

show subpopulations

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.:

AF XY:

0.201

AC XY:

14913

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.116

AC:

4829

AN:

41512

American (AMR)

AF:

0.233

AC:

3559

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

517

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1461

AN:

5176

South Asian (SAS)

AF:

0.138

AC:

665

AN:

4826

European-Finnish (FIN)

AF:

0.351

AC:

3709

AN:

10554

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14048

AN:

68004

Other (OTH)

AF:

0.180

AC:

379

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1173

2347

3520

4694

5867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.198

Hom.:

14262

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

(source)

DANN

Benign

0.79

PhyloP100

-3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over