dbSNP rs587777996: TNFRSF14:n.444G>A (chr1-2559725-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The ENST00000475523.5(TNFRSF14):n.444G>A 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 0.0325 in 1,538,132 control chromosomes in the GnomAD database, including 909 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 0.027 ( 74 hom., cov: 34)

Exomes 𝑓: 0.033 ( 835 hom. )

Consequence

TNFRSF14
ENST00000475523.5 non_coding_transcript_exon

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.66

Publications

3 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0265 (4042/152294) while in subpopulation NFE AF = 0.0385 (2620/68014). AF 95% confidence interval is 0.0373. There are 74 homozygotes in GnomAd4. There are 1968 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF14	NM_003820.4 link	c.305-98G>A		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.305-98G>A		intron_variant	Intron 3 of 7	1	NM_003820.4	ENSP00000347948.4		Q92956-1

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4043

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0508

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0247

AC:

3493

AN:

141290

AF XY:

0.0247

show subpopulations

Gnomad AFR exome

AF:

0.00409

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0438

Gnomad EAS exome

AF:

0.000268

Gnomad FIN exome

AF:

0.0563

Gnomad NFE exome

AF:

0.0373

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0332

AC:

45964

AN:

1385838

Hom.:

835

Cov.:

AF XY:

0.0326

AC XY:

22307

AN XY:

684054

show subpopulations

African (AFR)

AF:

0.00515

AC:

163

AN:

31680

American (AMR)

AF:

0.0169

AC:

605

AN:

35806

Ashkenazi Jewish (ASJ)

AF:

0.0414

AC:

1041

AN:

25174

East Asian (EAS)

AF:

0.000251

AC:

AN:

35886

South Asian (SAS)

AF:

0.00457

AC:

362

AN:

79286

European-Finnish (FIN)

AF:

0.0577

AC:

2026

AN:

35118

Middle Eastern (MID)

AF:

0.0182

AC:

104

AN:

5700

European-Non Finnish (NFE)

AF:

0.0370

AC:

39879

AN:

1079242

Other (OTH)

AF:

0.0306

AC:

1775

AN:

57946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3367

6734

10101

13468

16835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1468

2936

4404

5872

7340

<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:

0.0265

AC:

4042

AN:

152294

Hom.:

Cov.:

AF XY:

0.0264

AC XY:

1968

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00609

AC:

253

AN:

41568

American (AMR)

AF:

0.0271

AC:

414

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0508

AC:

540

AN:

10622

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0385

AC:

2620

AN:

68014

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

201

402

603

804

1005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0342

Hom.:

Bravo

AF:

0.0241

Asia WGS

AF:

0.00346

AC:

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

-0.89

CADD

Benign

2.4

(source)

DANN

Benign

0.43

PhyloP100

-1.7

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)

0.0

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over