17-16945825-A-G

Variant names:

• chr17-16945825-A-G
• rs4273077
• NM_012452.3:c.445+2913T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012452.3(TNFRSF13B):​c.445+2913T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,696 control chromosomes in the GnomAD database, including 1,730 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1730 hom., cov: 32)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 37 publications found

Genes affected

TNFRSF13B (HGNC:18153): (TNF receptor superfamily member 13B) The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

TNFRSF13B Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, G2P, Ambry Genetics
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307457 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	NM_012452.3	MANE Select	c.445+2913T>C		intron	N/A	NP_036584.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	ENST00000261652.7	TSL:1 MANE Select	c.445+2913T>C		intron	N/A	ENSP00000261652.2
	TNFRSF13B	ENST00000583789.1	TSL:1	c.307+2913T>C		intron	N/A	ENSP00000462952.1
	TNFRSF13B	ENST00000579315.5	TSL:3	c.445+2913T>C		intron	N/A	ENSP00000464069.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20345 AN: 151578 Hom.: 1726 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20364 AN: 151696 Hom.: 1730 Cov.: 32 AF XY: 0.139 AC XY: 10312 AN XY: 74150

African (AFR) AF: 0.132 AC: 5453 AN: 41296

American (AMR) AF: 0.189 AC: 2876 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2440 AN: 5146

South Asian (SAS) AF: 0.181 AC: 866 AN: 4796

European-Finnish (FIN) AF: 0.0969 AC: 1024 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6734 AN: 67866

Other (OTH) AF: 0.120 AC: 254 AN: 2108

Alfa AF: 0.121 Hom.: 4851

Bravo AF: 0.142

Asia WGS AF: 0.297 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.53
PhyloP100		0.0050
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4273077; hg19: chr17-16849139;