rs61972017

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-108306765-A-C
• chr13-108306765-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006573.5(TNFSF13B):​c.746-61A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 995,560 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (13 hom., cov: 28)
  • Exomes 𝑓: 0.015 (115 hom.)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0119 (1806/151490) while in subpopulation NFE AF = 0.0173 (1174/67776). AF 95% confidence interval is 0.0165. There are 13 homozygotes in GnomAd4. There are 867 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 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.746-61A>C		intron	N/A	NP_006564.1	Q9Y275-1
	TNFSF13B	NM_001145645.2		c.689-61A>C		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.746-61A>C		intron	N/A	ENSP00000365048.3	Q9Y275-1
	TNFSF13B	ENST00000430559.5	TSL:1	c.689-61A>C		intron	N/A	ENSP00000389540.1	Q9Y275-2
	TNFSF13B	ENST00000493765.1	TSL:2	n.300-61A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1807 AN: 151374 Hom.: 13 Cov.: 28

Gnomad AFR AF: 0.00361

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0140

GnomAD4 exome AF: 0.0151 AC: 12724 AN: 844070 Hom.: 115 AF XY: 0.0148 AC XY: 6479 AN XY: 438358

African (AFR) AF: 0.00261 AC: 47 AN: 17998

American (AMR) AF: 0.00814 AC: 241 AN: 29612

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 624 AN: 20214

East Asian (EAS) AF: 0.0000310 AC: 1 AN: 32290

South Asian (SAS) AF: 0.00272 AC: 169 AN: 62028

European-Finnish (FIN) AF: 0.0146 AC: 704 AN: 48342

Middle Eastern (MID) AF: 0.00136 AC: 6 AN: 4420

European-Non Finnish (NFE) AF: 0.0176 AC: 10391 AN: 590146

Other (OTH) AF: 0.0139 AC: 541 AN: 39020

GnomAD4 genome AF: 0.0119 AC: 1806 AN: 151490 Hom.: 13 Cov.: 28 AF XY: 0.0117 AC XY: 867 AN XY: 74018

African (AFR) AF: 0.00360 AC: 149 AN: 41378

American (AMR) AF: 0.0119 AC: 180 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 117 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4820

European-Finnish (FIN) AF: 0.0131 AC: 137 AN: 10440

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

European-Non Finnish (NFE) AF: 0.0173 AC: 1174 AN: 67776

Other (OTH) AF: 0.0139 AC: 29 AN: 2088

Alfa AF: 0.0156 Hom.: 0

Bravo AF: 0.0113

Asia WGS AF: 0.000868 AC: 3 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		-0.79
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs61972017;

hg19: chr13-108959113;