rs11570136

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-11964975-T-A
• chr16-11964975-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395854.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB2	NM_001395854.1		c.-536-949A>T		intron	N/A	NP_001382783.1
	NPIPB2	NM_001395855.1		c.-400-8738A>T		intron	N/A	NP_001382784.1
	NPIPB2	NM_001395852.1		c.-536-949A>T		intron	N/A	NP_001382781.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB2	ENST00000673243.1		c.-536-949A>T		intron	N/A	ENSP00000500799.1
	NPIPB2	ENST00000538896.5	TSL:5	c.-584+11593A>T		intron	N/A	ENSP00000442069.1
	NPIPB2	ENST00000532936.1	TSL:4	n.77-949A>T		intron	N/A

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

African (AFR) AF: 0.110 AC: 753 AN: 6836

American (AMR) AF: 0.169 AC: 1184 AN: 7000

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 2184 AN: 6888

East Asian (EAS) AF: 0.596 AC: 8676 AN: 14548

South Asian (SAS) AF: 0.458 AC: 7629 AN: 16656

European-Finnish (FIN) AF: 0.346 AC: 2673 AN: 7716

Middle Eastern (MID) AF: 0.333 AC: 305 AN: 916

European-Non Finnish (NFE) AF: 0.322 AC: 37526 AN: 116554

Other (OTH) AF: 0.309 AC: 3697 AN: 11954

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

African (AFR) AF: 0.116 AC: 4802 AN: 41546

American (AMR) AF: 0.183 AC: 2799 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3049 AN: 5176

South Asian (SAS) AF: 0.490 AC: 2358 AN: 4816

European-Finnish (FIN) AF: 0.390 AC: 4114 AN: 10562

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22355 AN: 67972

Other (OTH) AF: 0.254 AC: 536 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.51
PhyloP100		0.16
PromoterAI		-0.0045	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11570136; hg19: chr16-12058832;