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GeneBe

1-2556673-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003820.4(TNFRSF14):c.9T>C(p.Pro3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,609,744 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0061 ( 45 hom. )

Consequence

TNFRSF14
NM_003820.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07
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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-2556673-T-C is Benign according to our data. Variant chr1-2556673-T-C is described in ClinVar as [Benign]. Clinvar id is 787525.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.07 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNFRSF14NM_003820.4 linkuse as main transcriptc.9T>C p.Pro3= synonymous_variant 1/8 ENST00000355716.5
TNFRSF14-AS1NR_037844.2 linkuse as main transcriptn.59A>G non_coding_transcript_exon_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNFRSF14ENST00000355716.5 linkuse as main transcriptc.9T>C p.Pro3= synonymous_variant 1/81 NM_003820.4 P1Q92956-1
TNFRSF14-AS1ENST00000416860.3 linkuse as main transcriptn.79A>G non_coding_transcript_exon_variant 2/62

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00398
AC:
605
AN:
152200
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00142
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00150
Gnomad ASJ
AF:
0.00979
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00496
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00670
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00411
AC:
993
AN:
241854
Hom.:
5
AF XY:
0.00429
AC XY:
563
AN XY:
131302
show subpopulations
Gnomad AFR exome
AF:
0.00110
Gnomad AMR exome
AF:
0.00147
Gnomad ASJ exome
AF:
0.00837
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00553
Gnomad FIN exome
AF:
0.000249
Gnomad NFE exome
AF:
0.00605
Gnomad OTH exome
AF:
0.00272
GnomAD4 exome
AF:
0.00610
AC:
8886
AN:
1457426
Hom.:
45
Cov.:
30
AF XY:
0.00607
AC XY:
4396
AN XY:
724580
show subpopulations
Gnomad4 AFR exome
AF:
0.00117
Gnomad4 AMR exome
AF:
0.00165
Gnomad4 ASJ exome
AF:
0.00927
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00607
Gnomad4 FIN exome
AF:
0.000397
Gnomad4 NFE exome
AF:
0.00691
Gnomad4 OTH exome
AF:
0.00504
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00397
AC:
605
AN:
152318
Hom.:
3
Cov.:
33
AF XY:
0.00337
AC XY:
251
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00142
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00979
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00497
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00670
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00561
Hom.:
2
Bravo
AF:
0.00394
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
7.5
Dann
Benign
0.50

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.

Other links and lift over

dbSNP: rs11573967; hg19: chr1-2488112; COSMIC: COSV104672690; COSMIC: COSV104672690; API