17-16939194-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012452.3(TNFRSF13B):c.*353A>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 0.00346 in 231,240 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: TNFRSF13B NM_012452.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.231

Genes affected

TNFRSF13B (HGNC:18153): (TNF receptor superfamily member 13B) The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-16939194-T-G is Benign according to our data. Variant chr17-16939194-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 322020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF13B	NM_012452.3	c.*353A>C		3_prime_UTR_variant	5/5	ENST00000261652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.*353A>C		3_prime_UTR_variant	5/5	1	NM_012452.3	P2

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 523 AN: 152076 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00446

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00349 AC: 276 AN: 79046 Hom.: 0 Cov.: 0 AF XY: 0.00315 AC XY: 127 AN XY: 40348

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000400

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000868

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.00400

Gnomad4 OTH exome AF: 0.00332

GnomAD4 genome AF: 0.00344 AC: 523 AN: 152194 Hom.: 4 Cov.: 31 AF XY: 0.00425 AC XY: 316 AN XY: 74434

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.00446

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00329 Hom.: 1

Bravo AF: 0.00208

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Common Variable Immune Deficiency, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.6
Dann	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs56059714; hg19: chr17-16842508;