Genetic Variant TNFRSF14:n.485C>T (chr1-2559766-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 ENST00000475523.5(TNFRSF14):n.485C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,558,776 control chromosomes in the GnomAD database, including 214,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.58 ( 26835 hom., cov: 33)

Exomes 𝑓: 0.51 ( 188104 hom. )

Consequence

TNFRSF14
ENST00000475523.5 non_coding_transcript_exon

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.93

Publications

27 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 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF14	NM_003820.4 link	c.305-57C>T		intron_variant	Intron 3 of 7	ENST00000355716.5	NP_003811.2	Q92956-1A0A024R052

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5 link	c.305-57C>T		intron_variant	Intron 3 of 7	1	NM_003820.4	ENSP00000347948.4		Q92956-1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88150

AN:

151980

Hom.:

26787

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.651

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.548

GnomAD2 exomes

AF:

0.553

AC:

93669

AN:

169440

AF XY:

0.553

show subpopulations

Gnomad AFR exome

AF:

0.797

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.503

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.513

AC:

721736

AN:

1406678

Hom.:

188104

Cov.:

AF XY:

0.516

AC XY:

359477

AN XY:

696134

show subpopulations

African (AFR)

AF:

0.785

AC:

25607

AN:

32620

American (AMR)

AF:

0.544

AC:

20679

AN:

37982

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

11772

AN:

25346

East Asian (EAS)

AF:

0.524

AC:

19460

AN:

37160

South Asian (SAS)

AF:

0.640

AC:

51806

AN:

80994

European-Finnish (FIN)

AF:

0.492

AC:

19657

AN:

39960

Middle Eastern (MID)

AF:

0.548

AC:

3132

AN:

5712

European-Non Finnish (NFE)

AF:

0.495

AC:

538438

AN:

1088300

Other (OTH)

AF:

0.532

AC:

31185

AN:

58604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

24584

49168

73751

98335

122919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16072

32144

48216

64288

80360

<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:

0.580

AC:

88252

AN:

152098

Hom.:

26835

Cov.:

AF XY:

0.581

AC XY:

43204

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.768

AC:

31912

AN:

41526

American (AMR)

AF:

0.564

AC:

8620

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

1589

AN:

3472

East Asian (EAS)

AF:

0.543

AC:

2795

AN:

5150

South Asian (SAS)

AF:

0.652

AC:

3145

AN:

4826

European-Finnish (FIN)

AF:

0.510

AC:

5401

AN:

10586

Middle Eastern (MID)

AF:

0.514

AC:

150

AN:

292

European-Non Finnish (NFE)

AF:

0.489

AC:

33216

AN:

67932

Other (OTH)

AF:

0.553

AC:

1165

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1845

3690

5535

7380

9225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.445

Hom.:

2878

Bravo

AF:

0.584

Asia WGS

AF:

0.673

AC:

2343

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

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.97

(source)

DANN

Benign

0.37

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over