NM_003820.4:c.50A>G

Variant summary

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

The NM_003820.4(TNFRSF14):​c.50A>G​(p.Lys17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,602,598 control chromosomes in the GnomAD database, including 204,775 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.55 ( 24325 hom., cov: 33)
Exomes 𝑓: 0.49 ( 180450 hom. )

Consequence

TNFRSF14
NM_003820.4 missense

Scores

17

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.27

Publications

66 publications found
Variant links:
Genes affected
TNFRSF14 (HGNC:11912): (TNF receptor superfamily member 14) This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
TNFRSF14-AS1 (HGNC:26966): (TNFRSF14 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=2.6974876E-6).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNFRSF14NM_003820.4 linkc.50A>G p.Lys17Arg missense_variant Exon 1 of 8 ENST00000355716.5 NP_003811.2 Q92956-1A0A024R052

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNFRSF14ENST00000355716.5 linkc.50A>G p.Lys17Arg missense_variant Exon 1 of 8 1 NM_003820.4 ENSP00000347948.4 Q92956-1

Frequencies

GnomAD3 genomes
AF:
0.554
AC:
84223
AN:
151926
Hom.:
24294
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.719
Gnomad AMI
AF:
0.282
Gnomad AMR
AF:
0.538
Gnomad ASJ
AF:
0.452
Gnomad EAS
AF:
0.502
Gnomad SAS
AF:
0.639
Gnomad FIN
AF:
0.497
Gnomad MID
AF:
0.538
Gnomad NFE
AF:
0.474
Gnomad OTH
AF:
0.524
GnomAD2 exomes
AF:
0.514
AC:
121076
AN:
235732
AF XY:
0.514
show subpopulations
Gnomad AFR exome
AF:
0.727
Gnomad AMR exome
AF:
0.511
Gnomad ASJ exome
AF:
0.442
Gnomad EAS exome
AF:
0.491
Gnomad FIN exome
AF:
0.489
Gnomad NFE exome
AF:
0.467
Gnomad OTH exome
AF:
0.495
GnomAD4 exome
AF:
0.495
AC:
717835
AN:
1450556
Hom.:
180450
Cov.:
54
AF XY:
0.498
AC XY:
359180
AN XY:
720804
show subpopulations
African (AFR)
AF:
0.731
AC:
24212
AN:
33128
American (AMR)
AF:
0.511
AC:
22193
AN:
43448
Ashkenazi Jewish (ASJ)
AF:
0.454
AC:
11553
AN:
25422
East Asian (EAS)
AF:
0.489
AC:
19331
AN:
39534
South Asian (SAS)
AF:
0.624
AC:
52692
AN:
84504
European-Finnish (FIN)
AF:
0.479
AC:
25190
AN:
52592
Middle Eastern (MID)
AF:
0.539
AC:
3070
AN:
5696
European-Non Finnish (NFE)
AF:
0.478
AC:
528937
AN:
1106432
Other (OTH)
AF:
0.513
AC:
30657
AN:
59800
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
19073
38146
57218
76291
95364
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
15870
31740
47610
63480
79350
<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:
0.554
AC:
84301
AN:
152042
Hom.:
24325
Cov.:
33
AF XY:
0.556
AC XY:
41315
AN XY:
74308
show subpopulations
African (AFR)
AF:
0.719
AC:
29840
AN:
41492
American (AMR)
AF:
0.538
AC:
8229
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.452
AC:
1566
AN:
3468
East Asian (EAS)
AF:
0.501
AC:
2583
AN:
5158
South Asian (SAS)
AF:
0.640
AC:
3078
AN:
4808
European-Finnish (FIN)
AF:
0.497
AC:
5258
AN:
10572
Middle Eastern (MID)
AF:
0.524
AC:
154
AN:
294
European-Non Finnish (NFE)
AF:
0.474
AC:
32221
AN:
67944
Other (OTH)
AF:
0.529
AC:
1115
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1896
3793
5689
7586
9482
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
714
1428
2142
2856
3570
<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:
0.498
Hom.:
21797
Bravo
AF:
0.557
TwinsUK
AF:
0.492
AC:
1826
ALSPAC
AF:
0.479
AC:
1847
ESP6500AA
AF:
0.726
AC:
3193
ESP6500EA
AF:
0.472
AC:
4058
ExAC
AF:
0.510
AC:
61543
Asia WGS
AF:
0.637
AC:
2216
AN:
3478

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
Sep 19, 2013
ITMI
Significance:not provided
Review Status:no classification provided
Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
7.6
DANN
Benign
0.93
DEOGEN2
Benign
0.0079
T;T;T;T;.;T
Eigen
Benign
-0.96
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.014
N
MetaRNN
Benign
0.0000027
T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.2
.;.;.;.;.;L
PhyloP100
-1.3
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.59
N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.47
T;T;T;T;T;T
Sift4G
Benign
0.18
T;T;T;T;T;T
Polyphen
0.39
.;.;.;.;.;B
Vest4
0.030, 0.031
MPC
0.14
ClinPred
0.0080
T
GERP RS
-1.1
PromoterAI
0.030
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.033
gMVP
0.42
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs4870; hg19: chr1-2488153; COSMIC: COSV63186428; COSMIC: COSV63186428; API