rs148297590

Variant names:

• chr17-16972005-G-A
• rs148297590
• NM_012452.3:c.61+10C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-16972005-G-A
• chr17-16972005-G-C
• chr17-16972005-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012452.3(TNFRSF13B):​c.61+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,898 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (6 hom.)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.598
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-16972005-G-A is Benign according to our data. Variant chr17-16972005-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 322031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00574 (873/152204) while in subpopulation AFR AF = 0.0199 (828/41534). AF 95% confidence interval is 0.0188. There are 10 homozygotes in GnomAd4. There are 406 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.61+10C>T		intron_variant	Intron 1 of 4	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.61+10C>T		intron_variant	Intron 1 of 4	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 868 AN: 152086 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00172 AC: 432 AN: 251260 AF XY: 0.00124

Gnomad AFR exome AF: 0.0201

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000631 AC: 923 AN: 1461694 Hom.: 6 Cov.: 32 AF XY: 0.000549 AC XY: 399 AN XY: 727170

African (AFR) AF: 0.0187 AC: 626 AN: 33480

American (AMR) AF: 0.00253 AC: 113 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111950

Other (OTH) AF: 0.00179 AC: 108 AN: 60388

GnomAD4 genome AF: 0.00574 AC: 873 AN: 152204 Hom.: 10 Cov.: 32 AF XY: 0.00546 AC XY: 406 AN XY: 74412

African (AFR) AF: 0.0199 AC: 828 AN: 41534

American (AMR) AF: 0.00196 AC: 30 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68000

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00469 Hom.: 4

Bravo AF: 0.00675

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Sep 14, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The TNFRSF13B c.61+10C>T variant causes a missense change involving the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was found in the control population dataset of ExAC in 253/121068 control chromosomes (4 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.019068 (198/10384). This frequency is about 6674 times the estimated maximal expected allele frequency of a pathogenic TNFRSF13B variant (0.0000029), suggesting this is a benign polymorphism found primarily in the populations of African origin. In addition, one clinical diagnostic laboratory classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -

Oct 01, 2020

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunodeficiency, common variable, 2 Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Common Variable Immune Deficiency, Dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 05, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.4
DANN	Benign	0.87
PhyloP100		-0.60
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism

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: rs148297590; hg19: chr17-16875319;