rs151344628

Positions:

chr12-6329605-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001065.4(TNFRSF1A):c.1075C>T(p.Leu359Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 1,593,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

TNFRSF1A
NM_001065.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 2.99

Variant links:

Genes affected

TNFRSF1A (HGNC:11916): (TNF receptor superfamily member 1A) This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

TNFRSF1A links:

TNFRSF1A (HGNC:):

TNFRSF1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 12-6329605-G-A is Benign according to our data. Variant chr12-6329605-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 97422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6329605-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.99 with no splicing effect.

BS2

High AC in GnomAd4 at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF1A	NM_001065.4 linkuse as main transcript	c.1075C>T	p.Leu359Leu	synonymous_variant	10/10	ENST00000162749.7	NP_001056.1	P19438-1
TNFRSF1A	NM_001346091.2 linkuse as main transcript	c.751C>T	p.Leu251Leu	synonymous_variant	9/9		NP_001333020.1	P19438-2J9PH39
TNFRSF1A	NM_001346092.2 linkuse as main transcript	c.616C>T	p.Leu206Leu	synonymous_variant	11/11		NP_001333021.1	P19438
TNFRSF1A	NR_144351.2 linkuse as main transcript	n.1263C>T		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF1A	ENST00000162749.7 linkuse as main transcript	c.1075C>T	p.Leu359Leu	synonymous_variant	10/10	1	NM_001065.4	ENSP00000162749.2		P19438-1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000572

AC:

127

AN:

222140

Hom.:

AF XY:

0.000454

AC XY:

AN XY:

123276

show subpopulations

Gnomad AFR exome

AF:

0.000144

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000805

Gnomad NFE exome

AF:

0.000599

Gnomad OTH exome

AF:

0.00125

GnomAD4 exome

AF:

0.000647

AC:

933

AN:

1440942

Hom.:

Cov.:

AF XY:

0.000626

AC XY:

448

AN XY:

716146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000246

Gnomad4 NFE exome

AF:

0.000739

Gnomad4 OTH exome

AF:

0.000619

GnomAD4 genome

AF:

0.000499

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000714

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

TNF receptor-associated periodic fever syndrome (TRAPS)

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
not provided, no classification provided	literature only	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 24, 2012

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autoinflammatory syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.7

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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