17-16939598-A-G

Variant names:

• chr17-16939598-A-G
• rs11078355
• NM_012452.3:c.831T>C

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.831T>C​(p.Ser277Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,612,726 control chromosomes in the GnomAD database, including 168,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19706 hom., cov: 31)
  • Exomes 𝑓: 0.44 (149108 hom.)
• Consequence: TNFRSF13B NM_012452.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: -0.875
• Publications: 25 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

ENSG00000307457 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 17-16939598-A-G is Benign according to our data. Variant chr17-16939598-A-G is described in ClinVar as Benign. ClinVar VariationId is 260259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.875 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 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.831T>C	p.Ser277Ser	synonymous	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.831T>C	p.Ser277Ser	synonymous	Exon 5 of 5	ENSP00000261652.2	O14836-1
	TNFRSF13B	ENST00000583789.1	TSL:1	c.693T>C	p.Ser231Ser	synonymous	Exon 4 of 4	ENSP00000462952.1	O14836-2
	TNFRSF13B	ENST00000579315.5	TSL:3	c.446-6422T>C		intron	N/A	ENSP00000464069.1	J3QR67

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75120 AN: 151718 Hom.: 19662 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.463

GnomAD2 exomes AF: 0.495 AC: 122856 AN: 248314 AF XY: 0.492

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.798

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.442 AC: 645265 AN: 1460890 Hom.: 149108 Cov.: 52 AF XY: 0.446 AC XY: 324418 AN XY: 726644

African (AFR) AF: 0.622 AC: 20818 AN: 33468

American (AMR) AF: 0.559 AC: 24915 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 11833 AN: 26100

East Asian (EAS) AF: 0.830 AC: 32922 AN: 39680

South Asian (SAS) AF: 0.611 AC: 52584 AN: 86102

European-Finnish (FIN) AF: 0.358 AC: 19128 AN: 53404

Middle Eastern (MID) AF: 0.516 AC: 2971 AN: 5760

European-Non Finnish (NFE) AF: 0.406 AC: 451534 AN: 1111436

Other (OTH) AF: 0.473 AC: 28560 AN: 60342

GnomAD4 genome AF: 0.495 AC: 75222 AN: 151836 Hom.: 19706 Cov.: 31 AF XY: 0.499 AC XY: 36977 AN XY: 74172

African (AFR) AF: 0.612 AC: 25329 AN: 41386

American (AMR) AF: 0.540 AC: 8260 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1603 AN: 3464

East Asian (EAS) AF: 0.810 AC: 4155 AN: 5132

South Asian (SAS) AF: 0.610 AC: 2937 AN: 4812

European-Finnish (FIN) AF: 0.355 AC: 3742 AN: 10536

Middle Eastern (MID) AF: 0.462 AC: 134 AN: 290

European-Non Finnish (NFE) AF: 0.408 AC: 27738 AN: 67906

Other (OTH) AF: 0.466 AC: 983 AN: 2110

Alfa AF: 0.437 Hom.: 20236

Bravo AF: 0.514

Asia WGS AF: 0.708 AC: 2461 AN: 3478

EpiCase AF: 0.416

EpiControl AF: 0.417

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Immunodeficiency, common variable, 2 (2)
-	-	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	-0.96
CADD	Benign	0.53
DANN	Benign	0.37
PhyloP100		-0.88
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: rs11078355; hg19: chr17-16842912; COSMIC: COSV55425240; COSMIC: COSV55425240;