rs748127352

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001376887.1(TNFSF14):c.223G>C(p.Gly75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 1,564,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

TNFSF14
NM_001376887.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04221219).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376887.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFSF14	NM_001376887.1	MANE Select	c.223G>C	p.Gly75Arg	missense	Exon 2 of 4	NP_001363816.1	O43557-1
TNFSF14	NM_003807.5		c.223G>C	p.Gly75Arg	missense	Exon 3 of 5	NP_003798.2
TNFSF14	NM_172014.3		c.115G>C	p.Gly39Arg	missense	Exon 2 of 4	NP_742011.2	O43557-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFSF14	ENST00000675206.1	MANE Select	c.223G>C	p.Gly75Arg	missense	Exon 2 of 4	ENSP00000502837.1	O43557-1
TNFSF14	ENST00000599359.1	TSL:1	c.223G>C	p.Gly75Arg	missense	Exon 3 of 5	ENSP00000469049.1	O43557-1
TNFSF14	ENST00000245912.7	TSL:1	c.115G>C	p.Gly39Arg	missense	Exon 2 of 4	ENSP00000245912.3	O43557-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000492

AC:

AN:

203108

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000730

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000637

AC:

AN:

1411918

Hom.:

Cov.:

AF XY:

0.00000712

AC XY:

AN XY:

702418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29814

American (AMR)

AF:

0.00

AC:

AN:

30352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24166

East Asian (EAS)

AF:

0.00

AC:

AN:

36432

South Asian (SAS)

AF:

0.00

AC:

AN:

78370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00000821

AC:

AN:

1095884

Other (OTH)

AF:

0.00

AC:

AN:

58250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000282

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.50

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.20

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.32

M_CAP

Benign

0.0044

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.0

PhyloP100

-1.2

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.81

REVEL

Benign

0.013

Sift

Benign

0.13

Sift4G

Benign

0.26

Polyphen

0.0030

Vest4

0.074

MutPred

0.47

Gain of solvent accessibility (P = 0.0037)

MVP

0.35

MPC

0.40

ClinPred

0.89

GERP RS

-9.4

Varity_R

0.063

gMVP

0.33

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over