chr17-16948892-A-C

Variant names:

• chr17-16948892-A-C
• rs35062843
• NM_012452.3:c.291T>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.291T>G​(p.Pro97Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,614,174 control chromosomes in the GnomAD database, including 1,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (125 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1554 hom.)
• Consequence: TNFRSF13B NM_012452.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.313
• Publications: 10 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=-0.85).
• BP6: Variant 17-16948892-A-C is Benign according to our data. Variant chr17-16948892-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.313 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0965 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.291T>G	p.Pro97Pro	synonymous	Exon 3 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.291T>G	p.Pro97Pro	synonymous	Exon 3 of 5	ENSP00000261652.2	O14836-1
	TNFRSF13B	ENST00000583789.1	TSL:1	c.153T>G	p.Pro51Pro	synonymous	Exon 2 of 4	ENSP00000462952.1	O14836-2
	TNFRSF13B	ENST00000579315.5	TSL:3	c.291T>G	p.Pro97Pro	synonymous	Exon 3 of 4	ENSP00000464069.1	J3QR67

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5561 AN: 152176 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0483

GnomAD2 exomes AF: 0.0415 AC: 10448 AN: 251480 AF XY: 0.0443

Gnomad AFR exome AF: 0.0239

Gnomad AMR exome AF: 0.0383

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00799

Gnomad FIN exome AF: 0.0375

Gnomad NFE exome AF: 0.0373

Gnomad OTH exome AF: 0.0401

GnomAD4 exome AF: 0.0417 AC: 61000 AN: 1461880 Hom.: 1554 Cov.: 36 AF XY: 0.0434 AC XY: 31551 AN XY: 727240

African (AFR) AF: 0.0251 AC: 839 AN: 33480

American (AMR) AF: 0.0411 AC: 1837 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 288 AN: 26136

East Asian (EAS) AF: 0.00851 AC: 338 AN: 39700

South Asian (SAS) AF: 0.100 AC: 8652 AN: 86256

European-Finnish (FIN) AF: 0.0385 AC: 2055 AN: 53418

Middle Eastern (MID) AF: 0.0335 AC: 193 AN: 5768

European-Non Finnish (NFE) AF: 0.0398 AC: 44275 AN: 1112002

Other (OTH) AF: 0.0418 AC: 2523 AN: 60396

GnomAD4 genome AF: 0.0366 AC: 5572 AN: 152294 Hom.: 125 Cov.: 32 AF XY: 0.0375 AC XY: 2795 AN XY: 74480

African (AFR) AF: 0.0245 AC: 1019 AN: 41572

American (AMR) AF: 0.0551 AC: 842 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.00946 AC: 49 AN: 5182

South Asian (SAS) AF: 0.104 AC: 501 AN: 4818

European-Finnish (FIN) AF: 0.0331 AC: 351 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0383 AC: 2605 AN: 68032

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0349 Hom.: 54

Bravo AF: 0.0342

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.56
PhyloP100		-0.31
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: rs35062843; hg19: chr17-16852206;