rs3743591

Positions:

• chr16-11965175-A-G
• chr16-11965175-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395854.1(NPIPB2):​c.-536-1149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 904,702 control chromosomes in the GnomAD database, including 4,846 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 0.12 (1508 hom., cov: 33)
  • Exomes 𝑓: 0.071 (3338 hom.)
• Consequence: NPIPB2 NM_001395854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

Genes affected

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

NPIPB2 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF17	NM_001192.3	c.-150A>G		upstream_gene_variant		ENST00000053243.6	NP_001183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.-150A>G		upstream_gene_variant		1	NM_001192.3	ENSP00000053243.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17717 AN: 152134 Hom.: 1503 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0711 AC: 53477 AN: 752450 Hom.: 3338 Cov.: 10 AF XY: 0.0678 AC XY: 26303 AN XY: 388208

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.0993

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.0326

Gnomad4 FIN exome AF: 0.0899

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0815

GnomAD4 genome AF: 0.117 AC: 17744 AN: 152252 Hom.: 1508 Cov.: 33 AF XY: 0.118 AC XY: 8776 AN XY: 74446

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0310

Gnomad4 FIN AF: 0.0871

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0599 Hom.: 780

Bravo AF: 0.135

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
DANN	Benign	0.51

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: rs3743591; hg19: chr16-12059032; COSMIC: COSV50000494; COSMIC: COSV50000494;