Genetic Variant NPIPB2:c.-536-1155G>A (chr16-11965181-C-T) – 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.-536-1155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,026,146 control chromosomes in the GnomAD database, including 40,467 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 0.21 ( 4143 hom., cov: 33)

Exomes 𝑓: 0.27 ( 36324 hom. )

Consequence

NPIPB2
NM_001395854.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0770

Publications

12 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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3 link	c.-144C>T		upstream_gene_variant		ENST00000053243.6	NP_001183.2	Q02223-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF17	ENST00000053243.6 link	c.-144C>T		upstream_gene_variant		1	NM_001192.3	ENSP00000053243.1		Q02223-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31623

AN:

152088

Hom.:

4145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0717

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.0123

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.273

AC:

238711

AN:

873940

Hom.:

36324

Cov.:

AF XY:

0.269

AC XY:

119917

AN XY:

445296

show subpopulations

African (AFR)

AF:

0.0657

AC:

1388

AN:

21130

American (AMR)

AF:

0.152

AC:

4427

AN:

29212

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

4682

AN:

17482

East Asian (EAS)

AF:

0.0144

AC:

527

AN:

36592

South Asian (SAS)

AF:

0.135

AC:

7967

AN:

59092

European-Finnish (FIN)

AF:

0.222

AC:

8881

AN:

40000

Middle Eastern (MID)

AF:

0.225

AC:

844

AN:

3748

European-Non Finnish (NFE)

AF:

0.319

AC:

199675

AN:

626620

Other (OTH)

AF:

0.258

AC:

10320

AN:

40064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

8279

16558

24837

33116

41395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5008

10016

15024

20032

25040

<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:

0.208

AC:

31622

AN:

152206

Hom.:

4143

Cov.:

AF XY:

0.198

AC XY:

14770

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0716

AC:

2974

AN:

41554

American (AMR)

AF:

0.196

AC:

2990

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

895

AN:

3472

East Asian (EAS)

AF:

0.0122

AC:

AN:

5182

South Asian (SAS)

AF:

0.127

AC:

611

AN:

4816

European-Finnish (FIN)

AF:

0.214

AC:

2265

AN:

10604

Middle Eastern (MID)

AF:

0.192

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.309

AC:

21020

AN:

67990

Other (OTH)

AF:

0.246

AC:

520

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1227

2455

3682

4910

6137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.259

Hom.:

9020

Bravo

AF:

0.202

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.9

(source)

DANN

Benign

0.80

PhyloP100

-0.077

PromoterAI

0.021

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over