Genetic Variant TNFRSF14:c.304+606C>G (chr1-2559074-C-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_003820.4(TNFRSF14):c.304+606C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,368,990 control chromosomes in the GnomAD database, including 42 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 0.010 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 24 hom. )

Consequence

TNFRSF14
NM_003820.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -2.00

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.08).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0104 (1586/152334) while in subpopulation AFR AF = 0.0356 (1480/41570). AF 95% confidence interval is 0.0341. There are 18 homozygotes in GnomAd4. There are 734 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF14	NM_003820.4 link	c.304+606C>G		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.304+606C>G		intron_variant	Intron 3 of 7	1	NM_003820.4	ENSP00000347948.4		Q92956-1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1580

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00232

AC:

303

AN:

130366

AF XY:

0.00200

show subpopulations

Gnomad AFR exome

AF:

0.0371

Gnomad AMR exome

AF:

0.00259

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000607

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.00110

AC:

1343

AN:

1216656

Hom.:

Cov.:

AF XY:

0.000981

AC XY:

583

AN XY:

594314

show subpopulations

Gnomad4 AFR exome

AF:

0.0383

AC:

1081

AN:

28226

Gnomad4 AMR exome

AF:

0.00248

AC:

AN:

30658

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

21016

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

24100

Gnomad4 SAS exome

AF:

0.0000911

AC:

AN:

76824

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

12782

Gnomad4 NFE exome

AF:

0.0000340

AC:

AN:

969984

Gnomad4 Remaining exome

AF:

0.00295

AC:

142

AN:

48178

Heterozygous variant carriers

183

275

366

458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0104

AC:

1586

AN:

152334

Hom.:

Cov.:

AF XY:

0.00985

AC XY:

734

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0356

AC:

0.0356026

AN:

0.0356026

Gnomad4 AMR

AF:

0.00503

AC:

0.00502939

AN:

0.00502939

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000414

AC:

0.00041425

AN:

0.00041425

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000132

AC:

0.000132298

AN:

0.000132298

Gnomad4 OTH

AF:

0.00757

AC:

0.00756859

AN:

0.00756859

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000560

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00144

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

-0.99

CADD

Benign

0.36

DANN

Benign

0.45

Mutation Taster

=100/0

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over