chr13-108270208-G-A

Position:

chr13-108270208-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006573.5(TNFSF13B):c.313G>A(p.Ala105Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,602,924 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 23 hom. )

Consequence

TNFSF13B
NM_006573.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.103

Variant links:

Genes affected

TNFSF13B (HGNC:11929): (TNF superfamily member 13b) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFFR. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. It has been also shown to play an important role in the proliferation and differentiation of B cells. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

TNFSF13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027609766).

BP6

Variant 13-108270208-G-A is Benign according to our data. Variant chr13-108270208-G-A is described in ClinVar as [Benign]. Clinvar id is 791367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000958 (1390/1450598) while in subpopulation AMR AF= 0.0206 (916/44398). AF 95% confidence interval is 0.0195. There are 23 homozygotes in gnomad4_exome. There are 621 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNFSF13B	NM_006573.5 linkuse as main transcript	c.313G>A	p.Ala105Thr	missense_variant	1/6	ENST00000375887.9
TNFSF13B	NM_001145645.2 linkuse as main transcript	c.313G>A	p.Ala105Thr	missense_variant	1/5
TNFSF13B	XM_047430055.1 linkuse as main transcript	c.313G>A	p.Ala105Thr	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13B	ENST00000375887.9 linkuse as main transcript	c.313G>A	p.Ala105Thr	missense_variant	1/6	1	NM_006573.5	P1	Q9Y275-1

Frequencies

GnomAD3 genomes

AF:

0.00182

AC:

277

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00733

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00366

AC:

873

AN:

238444

Hom.:

AF XY:

0.00294

AC XY:

382

AN XY:

130066

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.00113

Gnomad EAS exome

AF:

0.00788

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.000958

AC:

1390

AN:

1450598

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

621

AN XY:

721694

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.00174

Gnomad4 EAS exome

AF:

0.00787

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00182

AC:

277

AN:

152326

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00735

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000406

Hom.:

Bravo

AF:

0.00279

ExAC

AF:

0.00250

AC:

304

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.19

.;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.42

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.035

MVP

0.11

MPC

0.47

ClinPred

0.0078

GERP RS

1.9

Varity_R

0.029

gMVP

0.18

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