chr13-108303585-T-C

Variant names:

• chr13-108303585-T-C
• rs77273581
• NM_006573.5:c.726T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006573.5(TNFSF13B):​c.726T>C​(p.Asn242Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000886 in 1,612,992 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (3 hom.)
• Consequence: TNFSF13B NM_006573.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.102
• Publications: 2 publications found

Genes affected

TNFSF13B (HGNC:11929): (TNF superfamily member 13b) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFFR. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. It has been also shown to play an important role in the proliferation and differentiation of B cells. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 13-108303585-T-C is Benign according to our data. Variant chr13-108303585-T-C is described in ClinVar as Benign. ClinVar VariationId is 783680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.102 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00483 (735/152290) while in subpopulation AFR AF = 0.0167 (696/41562). AF 95% confidence interval is 0.0157. There are 4 homozygotes in GnomAd4. There are 339 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006573.5. 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
	TNFSF13B	NM_006573.5	MANE Select	c.726T>C	p.Asn242Asn	synonymous	Exon 5 of 6	NP_006564.1	Q9Y275-1
	TNFSF13B	NM_001145645.2		c.669T>C	p.Asn223Asn	synonymous	Exon 4 of 5	NP_001139117.1	Q9Y275-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF13B	ENST00000375887.9	TSL:1 MANE Select	c.726T>C	p.Asn242Asn	synonymous	Exon 5 of 6	ENSP00000365048.3	Q9Y275-1
	TNFSF13B	ENST00000430559.5	TSL:1	c.669T>C	p.Asn223Asn	synonymous	Exon 4 of 5	ENSP00000389540.1	Q9Y275-2
	TNFSF13B	ENST00000479435.1	TSL:3	n.618T>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 734 AN: 152172 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00117 AC: 292 AN: 249858 AF XY: 0.000904

Gnomad AFR exome AF: 0.0157

Gnomad AMR exome AF: 0.000553

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000475 AC: 694 AN: 1460702 Hom.: 3 Cov.: 32 AF XY: 0.000446 AC XY: 324 AN XY: 726590

African (AFR) AF: 0.0165 AC: 551 AN: 33410

American (AMR) AF: 0.000650 AC: 29 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5748

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111540

Other (OTH) AF: 0.00128 AC: 77 AN: 60340

GnomAD4 genome AF: 0.00483 AC: 735 AN: 152290 Hom.: 4 Cov.: 32 AF XY: 0.00455 AC XY: 339 AN XY: 74462

African (AFR) AF: 0.0167 AC: 696 AN: 41562

American (AMR) AF: 0.00164 AC: 25 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00185 Hom.: 0

Bravo AF: 0.00549

Asia WGS AF: 0.00202 AC: 7 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		-0.10
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: rs77273581; hg19: chr13-108955933;