13-108306732-ATTT-ATTTTTTT

Variant names:

• chr13-108306732-A-ATTTT
• rs11381410
• NM_006573.5:c.746-87_746-84dupTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006573.5(TNFSF13B):​c.746-87_746-84dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 437,060 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.746-87_746-84dupTTTT		intron	N/A	NP_006564.1	Q9Y275-1
	TNFSF13B	NM_001145645.2		c.689-87_689-84dupTTTT		intron	N/A	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.746-94_746-93insTTTT		intron	N/A	ENSP00000365048.3	Q9Y275-1
	TNFSF13B	ENST00000430559.5	TSL:1	c.689-94_689-93insTTTT		intron	N/A	ENSP00000389540.1	Q9Y275-2
	TNFSF13B	ENST00000493765.1	TSL:2	n.300-94_300-93insTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149332 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000229 AC: 1 AN: 437060 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 230962

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9216

American (AMR) AF: 0.0000750 AC: 1 AN: 13332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12278

East Asian (EAS) AF: 0.00 AC: 0 AN: 21522

South Asian (SAS) AF: 0.00 AC: 0 AN: 37746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2636

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 286310

Other (OTH) AF: 0.00 AC: 0 AN: 22810

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149332 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72792

African (AFR) AF: 0.00 AC: 0 AN: 40822

American (AMR) AF: 0.00 AC: 0 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67160

Other (OTH) AF: 0.00 AC: 0 AN: 2030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11381410; hg19: chr13-108959080;