rs56153623

Variant names:

• chr17-16939374-C-T
• rs56153623
• NM_012452.3:c.*173G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012452.3(TNFRSF13B):​c.*173G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 738,034 control chromosomes in the GnomAD database, including 49,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11763 hom., cov: 28)
  • Exomes 𝑓: 0.35 (38099 hom.)
• Consequence: TNFRSF13B NM_012452.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.56
• Publications: 7 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: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307457 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-16939374-C-T is Benign according to our data. Variant chr17-16939374-C-T is described in ClinVar as Benign. ClinVar VariationId is 322022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	NM_012452.3	MANE Select	c.*173G>A		3_prime_UTR	Exon 5 of 5	NP_036584.1	O14836-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	ENST00000261652.7	TSL:1 MANE Select	c.*173G>A		3_prime_UTR	Exon 5 of 5	ENSP00000261652.2	O14836-1
	TNFRSF13B	ENST00000579315.5	TSL:3	c.446-6198G>A		intron	N/A	ENSP00000464069.1	J3QR67
	TNFRSF13B	ENST00000579009.1	TSL:6	n.1689G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 58707 AN: 150492 Hom.: 11741 Cov.: 28

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.350 AC: 205332 AN: 587424 Hom.: 38099 Cov.: 8 AF XY: 0.351 AC XY: 104426 AN XY: 297154

African (AFR) AF: 0.473 AC: 6694 AN: 14160

American (AMR) AF: 0.390 AC: 5606 AN: 14382

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 5326 AN: 13622

East Asian (EAS) AF: 0.565 AC: 15626 AN: 27660

South Asian (SAS) AF: 0.382 AC: 13937 AN: 36458

European-Finnish (FIN) AF: 0.291 AC: 8438 AN: 28976

Middle Eastern (MID) AF: 0.415 AC: 942 AN: 2272

European-Non Finnish (NFE) AF: 0.328 AC: 137762 AN: 420188

Other (OTH) AF: 0.370 AC: 11001 AN: 29706

GnomAD4 genome AF: 0.390 AC: 58780 AN: 150610 Hom.: 11763 Cov.: 28 AF XY: 0.391 AC XY: 28748 AN XY: 73508

African (AFR) AF: 0.474 AC: 19387 AN: 40900

American (AMR) AF: 0.413 AC: 6257 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1385 AN: 3466

East Asian (EAS) AF: 0.536 AC: 2701 AN: 5038

South Asian (SAS) AF: 0.386 AC: 1823 AN: 4718

European-Finnish (FIN) AF: 0.293 AC: 3066 AN: 10462

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 22979 AN: 67580

Other (OTH) AF: 0.369 AC: 771 AN: 2088

Alfa AF: 0.369 Hom.: 1388

Bravo AF: 0.404

Asia WGS AF: 0.444 AC: 1545 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Common Variable Immune Deficiency, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.21
PhyloP100		-2.6
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: rs56153623; hg19: chr17-16842688; COSMIC: COSV55425237; COSMIC: COSV55425237;