Genetic Variant NPIPB2:c.-536-949A>T (chr16-11964975-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.156

Publications

9 publications found

Variant links:

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 links:

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]

TNFRSF17 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
NPIPB2	NM_001395854.1	c.-536-949A>T	intron	N/A	NP_001382783.1	A0A5F9ZI19
NPIPB2	NM_001395855.1	c.-400-8738A>T	intron	N/A	NP_001382784.1	A0A5F9ZI19
NPIPB2	NM_001395852.1	c.-536-949A>T	intron	N/A	NP_001382781.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPIPB2	ENST00000673243.1		c.-536-949A>T	intron	N/A	ENSP00000500799.1	A0A5F9ZI19
NPIPB2	ENST00000538896.5	TSL:5	c.-584+11593A>T	intron	N/A	ENSP00000442069.1	F5H898
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.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1872

3744

5617

7489

9361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.273

AC:

41481

AN:

152126

Hom.:

6843

Cov.:

AF XY:

0.279

AC XY:

20717

AN XY:

74338

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1439

2878

4317

5756

7195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.51

PhyloP100

0.16

PromoterAI

-0.0045

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over