NM_001395854.1:c.-536-949A>T

Variant names:

• chr16-11964975-T-A
• rs11570136
• NM_001395854.1:c.-536-949A>T

Variant summary

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

The NM_001395854.1(NPIPB2):​c.-536-949A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 341,194 control chromosomes in the GnomAD database, including 19,342 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 0.27 (6843 hom., cov: 32)
  • Exomes 𝑓: 0.34 (12499 hom.)
• Consequence: NPIPB2 NM_001395854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

Genes affected

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

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3	c.-350T>A		upstream_gene_variant		ENST00000053243.6	NP_001183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.-350T>A		upstream_gene_variant		1	NM_001192.3	ENSP00000053243.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41478 AN: 152006 Hom.: 6847 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.342 AC: 64627 AN: 189068 Hom.: 12499 AF XY: 0.349 AC XY: 33579 AN XY: 96262

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.273 AC: 41481 AN: 152126 Hom.: 6843 Cov.: 32 AF XY: 0.279 AC XY: 20717 AN XY: 74338

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.254

Alfa AF: 0.283 Hom.: 805

Bravo AF: 0.246

Asia WGS AF: 0.443 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11570136; hg19: chr16-12058832;