rs7290134

Variant names:

• chr22-41925247-A-G
• rs7290134
• NM_052945.4:c.*120T>C

Variant summary

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

The NM_052945.4(TNFRSF13C):​c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,103,354 control chromosomes in the GnomAD database, including 55,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (18242 hom., cov: 32)
  • Exomes 𝑓: 0.25 (37108 hom.)
• Consequence: TNFRSF13C NM_052945.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.681
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-41925247-A-G is Benign according to our data. Variant chr22-41925247-A-G is described in ClinVar as Benign. ClinVar VariationId is 341874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

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.*120T>C		3_prime_UTR	Exon 3 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.*120T>C		3_prime_UTR	Exon 3 of 3	ENSP00000291232.3
	TNFRSF13C	ENST00000898406.1		c.*120T>C		3_prime_UTR	Exon 3 of 3	ENSP00000568465.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62078 AN: 152016 Hom.: 18175 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.253 AC: 241121 AN: 951220 Hom.: 37108 Cov.: 12 AF XY: 0.254 AC XY: 120678 AN XY: 475028

African (AFR) AF: 0.840 AC: 18565 AN: 22112

American (AMR) AF: 0.547 AC: 12873 AN: 23542

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 4977 AN: 17602

East Asian (EAS) AF: 0.105 AC: 3508 AN: 33388

South Asian (SAS) AF: 0.348 AC: 20541 AN: 58970

European-Finnish (FIN) AF: 0.204 AC: 6192 AN: 30378

Middle Eastern (MID) AF: 0.302 AC: 901 AN: 2986

European-Non Finnish (NFE) AF: 0.224 AC: 161155 AN: 719580

Other (OTH) AF: 0.291 AC: 12409 AN: 42662

GnomAD4 genome AF: 0.409 AC: 62198 AN: 152134 Hom.: 18242 Cov.: 32 AF XY: 0.405 AC XY: 30145 AN XY: 74372

African (AFR) AF: 0.818 AC: 33917 AN: 41488

American (AMR) AF: 0.462 AC: 7053 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.117 AC: 608 AN: 5176

South Asian (SAS) AF: 0.358 AC: 1727 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10590

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14816 AN: 67990

Other (OTH) AF: 0.371 AC: 783 AN: 2110

Alfa AF: 0.305 Hom.: 4056

Bravo AF: 0.448

Asia WGS AF: 0.283 AC: 982 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	Immunodeficiency, common variable, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.52
PhyloP100		0.68
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: rs7290134; hg19: chr22-42321251; COSMIC: COSV52170161; COSMIC: COSV52170161;