rs373828157

Variant names:

• chr22-41926714-G-A
• rs373828157
• NM_052945.4:c.60C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-41926714-G-A
• chr22-41926714-G-C
• chr22-41926714-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_052945.4(TNFRSF13C):​c.60C>T​(p.Val20Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,449,040 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (40 hom.)
• Consequence: TNFRSF13C NM_052945.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:4
• Conservation: PhyloP100: -0.168
• Publications: 0 publications found

Genes affected

TNFRSF13C (HGNC:17755): (TNF receptor superfamily member 13C) B cell-activating factor (BAFF) enhances B-cell survival in vitro and is a regulator of the peripheral B-cell population. Overexpression of Baff in mice results in mature B-cell hyperplasia and symptoms of systemic lupus erythematosus (SLE). Also, some SLE patients have increased levels of BAFF in serum. Therefore, it has been proposed that abnormally high levels of BAFF may contribute to the pathogenesis of autoimmune diseases by enhancing the survival of autoreactive B cells. The protein encoded by this gene is a receptor for BAFF and is a type III transmembrane protein containing a single extracellular cysteine-rich domain. It is thought that this receptor is the principal receptor required for BAFF-mediated mature B-cell survival. [provided by RefSeq, Jul 2008]

TNFRSF13C Gene-Disease associations (from GenCC):

• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency, common variable, 4

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-41926714-G-A is Benign according to our data. Variant chr22-41926714-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 440344.
• BP7: Synonymous conserved (PhyloP=-0.168 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 40 AD,AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052945.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13C	NM_052945.4	MANE Select	c.60C>T	p.Val20Val	synonymous	Exon 1 of 3	NP_443177.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13C	ENST00000291232.5	TSL:1 MANE Select	c.60C>T	p.Val20Val	synonymous	Exon 1 of 3	ENSP00000291232.3

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 574 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00674

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00377 AC: 254 AN: 67386 AF XY: 0.00332

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.000860

Gnomad ASJ exome AF: 0.00168

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00823

Gnomad OTH exome AF: 0.00500

GnomAD4 exome AF: 0.00607 AC: 7872 AN: 1296828 Hom.: 40 Cov.: 33 AF XY: 0.00587 AC XY: 3745 AN XY: 638150

African (AFR) AF: 0.00122 AC: 32 AN: 26174

American (AMR) AF: 0.000961 AC: 23 AN: 23930

Ashkenazi Jewish (ASJ) AF: 0.00160 AC: 36 AN: 22512

East Asian (EAS) AF: 0.0000358 AC: 1 AN: 27900

South Asian (SAS) AF: 0.000896 AC: 62 AN: 69218

European-Finnish (FIN) AF: 0.00114 AC: 37 AN: 32396

Middle Eastern (MID) AF: 0.000260 AC: 1 AN: 3852

European-Non Finnish (NFE) AF: 0.00722 AC: 7491 AN: 1037220

Other (OTH) AF: 0.00352 AC: 189 AN: 53626

GnomAD4 genome AF: 0.00377 AC: 574 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.00345 AC XY: 257 AN XY: 74424

African (AFR) AF: 0.00108 AC: 45 AN: 41572

American (AMR) AF: 0.00105 AC: 16 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.000378 AC: 4 AN: 10592

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00674 AC: 458 AN: 67978

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00144 Hom.: 0

Bravo AF: 0.00388

Asia WGS AF: 0.000869 AC: 3 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	Immunodeficiency, common variable, 4 (3)
-	-	1	not provided (1)
-	-	1	TNFRSF13C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.93
PhyloP100		-0.17
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: rs373828157; hg19: chr22-42322718;