rs2071336

Positions:

• chr16-11967817-G-A
• chr16-11967817-G-C
• chr16-11967817-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001192.3(TNFRSF17):​c.525G>A​(p.Thr175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 1,613,968 control chromosomes in the GnomAD database, including 2,728 homozygotes. 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: 𝑓 0.052 (334 hom., cov: 32)
  • Exomes 𝑓: 0.040 (2394 hom.)
• Consequence: TNFRSF17 NM_001192.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

Genes affected

TNFRSF17 (HGNC:11913): (TNF receptor superfamily member 17) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation. [provided by RefSeq, Jul 2008]

NPIPB2 (HGNC:37451): (nuclear pore complex interacting protein family member B2) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.363 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF17	NM_001192.3	c.525G>A	p.Thr175=	synonymous_variant	3/3	ENST00000053243.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.525G>A	p.Thr175=	synonymous_variant	3/3	1	NM_001192.3	P1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7895 AN: 152090 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0479

GnomAD3 exomes AF: 0.0680 AC: 17092 AN: 251210 Hom.: 1403 AF XY: 0.0598 AC XY: 8115 AN XY: 135778

Gnomad AFR exome AF: 0.0603

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.0744

Gnomad EAS exome AF: 0.0700

Gnomad SAS exome AF: 0.0167

Gnomad FIN exome AF: 0.0402

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0570

GnomAD4 exome AF: 0.0402 AC: 58825 AN: 1461760 Hom.: 2394 Cov.: 31 AF XY: 0.0390 AC XY: 28336 AN XY: 727150

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.0751

Gnomad4 EAS exome AF: 0.0882

Gnomad4 SAS exome AF: 0.0184

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0313

Gnomad4 OTH exome AF: 0.0411

GnomAD4 genome AF: 0.0519 AC: 7900 AN: 152208 Hom.: 334 Cov.: 32 AF XY: 0.0531 AC XY: 3948 AN XY: 74414

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0829

Gnomad4 EAS AF: 0.0694

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0474

Alfa AF: 0.0468 Hom.: 254

Bravo AF: 0.0643

Asia WGS AF: 0.0500 AC: 175 AN: 3478

EpiCase AF: 0.0321

EpiControl AF: 0.0329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.8
DANN	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071336; hg19: chr16-12061674; COSMIC: COSV50000996; COSMIC: COSV50000996;