rs8072293

Variant names:

• chr17-16952564-C-T
• rs8072293
• NM_012452.3:c.81G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-16952564-C-T
• chr17-16952564-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012452.3(TNFRSF13B):​c.81G>A​(p.Thr27Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,614,088 control chromosomes in the GnomAD database, including 483,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51755 hom., cov: 33)
  • Exomes 𝑓: 0.77 (431762 hom.)
• Consequence: TNFRSF13B NM_012452.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9 O:1
• Conservation: PhyloP100: -1.98
• Publications: 27 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), Ambry Genetics, Laboratory for Molecular Medicine, G2P, ClinGen
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-16952564-C-T is Benign according to our data. Variant chr17-16952564-C-T is described in ClinVar as Benign. ClinVar VariationId is 36879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.81G>A	p.Thr27Thr	synonymous	Exon 2 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.81G>A	p.Thr27Thr	synonymous	Exon 2 of 5	ENSP00000261652.2	O14836-1
	TNFRSF13B	ENST00000583789.1	TSL:1	c.62-3581G>A		intron	N/A	ENSP00000462952.1	O14836-2
	TNFRSF13B	ENST00000579315.5	TSL:3	c.81G>A	p.Thr27Thr	synonymous	Exon 2 of 4	ENSP00000464069.1	J3QR67

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124657 AN: 152150 Hom.: 51691 Cov.: 33

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.795

GnomAD2 exomes AF: 0.806 AC: 202612 AN: 251260 AF XY: 0.802

Gnomad AFR exome AF: 0.953

Gnomad AMR exome AF: 0.842

Gnomad ASJ exome AF: 0.712

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.747

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.766 AC: 1119956 AN: 1461820 Hom.: 431762 Cov.: 74 AF XY: 0.767 AC XY: 557826 AN XY: 727206

African (AFR) AF: 0.953 AC: 31922 AN: 33480

American (AMR) AF: 0.837 AC: 37424 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 18524 AN: 26136

East Asian (EAS) AF: 0.999 AC: 39677 AN: 39700

South Asian (SAS) AF: 0.840 AC: 72466 AN: 86258

European-Finnish (FIN) AF: 0.782 AC: 41743 AN: 53408

Middle Eastern (MID) AF: 0.747 AC: 4310 AN: 5768

European-Non Finnish (NFE) AF: 0.744 AC: 827204 AN: 1111958

Other (OTH) AF: 0.773 AC: 46686 AN: 60392

GnomAD4 genome AF: 0.819 AC: 124783 AN: 152268 Hom.: 51755 Cov.: 33 AF XY: 0.824 AC XY: 61331 AN XY: 74444

African (AFR) AF: 0.947 AC: 39372 AN: 41562

American (AMR) AF: 0.804 AC: 12295 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2365 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5174 AN: 5188

South Asian (SAS) AF: 0.850 AC: 4103 AN: 4826

European-Finnish (FIN) AF: 0.785 AC: 8328 AN: 10614

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50448 AN: 67986

Other (OTH) AF: 0.797 AC: 1686 AN: 2116

Alfa AF: 0.771 Hom.: 139377

Bravo AF: 0.825

Asia WGS AF: 0.928 AC: 3229 AN: 3478

EpiCase AF: 0.743

EpiControl AF: 0.739

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Immunodeficiency, common variable, 2 (3)
-	-	3	not specified (3)
-	-	2	not provided (3)
-	-	1	Common Variable Immune Deficiency, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs8072293; hg19: chr17-16855878; COSMIC: COSV108022591;