dbSNP rs2281852: TNFRSF14:c.305-320C>A (chr1-2559503-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003820.4(TNFRSF14):c.305-320C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 1,472,328 control chromosomes in the GnomAD database, including 191,666 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 0.54 ( 22913 hom., cov: 34)

Exomes 𝑓: 0.50 ( 168753 hom. )

Consequence

TNFRSF14
NM_003820.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.90

Publications

24 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:

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 (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	NM_003820.4	MANE Select	c.305-320C>A		intron	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.305-320C>A		intron	N/A	NP_001284534.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNFRSF14	ENST00000355716.5	TSL:1 MANE Select	c.305-320C>A	intron	N/A	ENSP00000347948.4	Q92956-1
TNFRSF14	ENST00000475523.5	TSL:1	n.222C>A	non_coding_transcript_exon	Exon 2 of 6
TNFRSF14	ENST00000860787.1		c.305-56C>A	intron	N/A	ENSP00000530846.1

Frequencies

GnomAD3 genomes

AF:

0.543

AC:

82469

AN:

151920

Hom.:

22890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.521

GnomAD2 exomes

AF:

0.525

AC:

70597

AN:

134594

AF XY:

0.528

show subpopulations

Gnomad AFR exome

AF:

0.659

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.479

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.503

AC:

663495

AN:

1320290

Hom.:

168753

Cov.:

AF XY:

0.506

AC XY:

328096

AN XY:

648554

show subpopulations

African (AFR)

AF:

0.661

AC:

20283

AN:

30680

American (AMR)

AF:

0.531

AC:

17795

AN:

33536

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

11002

AN:

23790

East Asian (EAS)

AF:

0.493

AC:

15109

AN:

30642

South Asian (SAS)

AF:

0.626

AC:

48670

AN:

77808

European-Finnish (FIN)

AF:

0.481

AC:

12426

AN:

25820

Middle Eastern (MID)

AF:

0.536

AC:

2901

AN:

5412

European-Non Finnish (NFE)

AF:

0.489

AC:

507161

AN:

1038102

Other (OTH)

AF:

0.516

AC:

28148

AN:

54500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

19230

38460

57689

76919

96149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15746

31492

47238

62984

78730

<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:

0.543

AC:

82536

AN:

152038

Hom.:

22913

Cov.:

AF XY:

0.545

AC XY:

40536

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.655

AC:

27156

AN:

41468

American (AMR)

AF:

0.550

AC:

8406

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

1583

AN:

3472

East Asian (EAS)

AF:

0.503

AC:

2599

AN:

5172

South Asian (SAS)

AF:

0.642

AC:

3096

AN:

4824

European-Finnish (FIN)

AF:

0.508

AC:

5373

AN:

10572

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32807

AN:

67920

Other (OTH)

AF:

0.525

AC:

1107

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1901

3803

5704

7606

9507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.438

Hom.:

3679

Bravo

AF:

0.542

Asia WGS

AF:

0.637

AC:

2216

AN:

3478

ClinVar

ClinVar submissions

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.62

(source)

DANN

Benign

0.26

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)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over