rs11652843

Variant names:

• chr17-16939936-A-C
• rs11652843
• NM_012452.3:c.632-139T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-16939936-A-C
• chr17-16939936-A-G
• chr17-16939936-A-T

Variant summary

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

The NM_012452.3(TNFRSF13B):​c.632-139T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,241,898 control chromosomes in the GnomAD database, including 38,900 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 0.19 (3373 hom., cov: 33)
  • Exomes 𝑓: 0.25 (35527 hom.)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.632-139T>G		intron_variant	Intron 4 of 4	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.632-139T>G		intron_variant	Intron 4 of 4	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28561 AN: 152094 Hom.: 3375 Cov.: 33

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.247 AC: 269313 AN: 1089686 Hom.: 35527 Cov.: 15 AF XY: 0.245 AC XY: 130918 AN XY: 533878

African (AFR) AF: 0.0479 AC: 1162 AN: 24256

American (AMR) AF: 0.185 AC: 3498 AN: 18942

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 5238 AN: 17558

East Asian (EAS) AF: 0.000595 AC: 20 AN: 33602

South Asian (SAS) AF: 0.158 AC: 9050 AN: 57156

European-Finnish (FIN) AF: 0.222 AC: 6713 AN: 30190

Middle Eastern (MID) AF: 0.280 AC: 898 AN: 3204

European-Non Finnish (NFE) AF: 0.270 AC: 231657 AN: 857972

Other (OTH) AF: 0.237 AC: 11077 AN: 46806

GnomAD4 genome AF: 0.188 AC: 28555 AN: 152212 Hom.: 3373 Cov.: 33 AF XY: 0.182 AC XY: 13578 AN XY: 74432

African (AFR) AF: 0.0547 AC: 2275 AN: 41554

American (AMR) AF: 0.208 AC: 3181 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3472

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5182

South Asian (SAS) AF: 0.149 AC: 719 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2302 AN: 10606

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18281 AN: 67960

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.132 Hom.: 245

Bravo AF: 0.182

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.29
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11652843; hg19: chr17-16843250; COSMIC: COSV55430920; COSMIC: COSV55430920;