chr13-108306765-A-T

Variant names:

• chr13-108306765-A-T
• rs61972017
• NM_006573.5:c.746-61A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006573.5(TNFSF13B):​c.746-61A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 844,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.746-61A>T		intron_variant	Intron 5 of 5	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.689-61A>T		intron_variant	Intron 4 of 4		NP_001139117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.746-61A>T		intron_variant	Intron 5 of 5	1	NM_006573.5	ENSP00000365048.3
TNFSF13B	ENST00000430559.5	c.689-61A>T		intron_variant	Intron 4 of 4	1		ENSP00000389540.1
TNFSF13B	ENST00000493765.1	n.300-61A>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 844208 Hom.: 0 AF XY: 0.00000228 AC XY: 1 AN XY: 438430

⚠️ 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: 17998

American (AMR) AF: 0.00 AC: 0 AN: 29616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20220

East Asian (EAS) AF: 0.00 AC: 0 AN: 32290

South Asian (SAS) AF: 0.00 AC: 0 AN: 62030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4420

European-Non Finnish (NFE) AF: 0.00000169 AC: 1 AN: 590260

Other (OTH) AF: 0.00 AC: 0 AN: 39028

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.65
PhyloP100		-0.79

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: rs61972017; hg19: chr13-108959113;