dbSNP rs3743591: NPIPB2:c.-536-1149T>C (chr16-11965175-A-G) – 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.-536-1149T>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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

10 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=-0.81).

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 rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3 link	c.-150A>G		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.-150A>G		upstream_gene_variant		1	NM_001192.3	ENSP00000053243.1		Q02223-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17717

AN:

152134

Hom.:

1503

Cov.:

show subpopulations

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.:

AF XY:

0.0678

AC XY:

26303

AN XY:

388208

show subpopulations

African (AFR)

AF:

0.217

AC:

4028

AN:

18596

American (AMR)

AF:

0.289

AC:

7851

AN:

27160

Ashkenazi Jewish (ASJ)

AF:

0.0993

AC:

1621

AN:

16324

East Asian (EAS)

AF:

0.169

AC:

6075

AN:

35960

South Asian (SAS)

AF:

0.0326

AC:

1814

AN:

55728

European-Finnish (FIN)

AF:

0.0899

AC:

3519

AN:

39164

Middle Eastern (MID)

AF:

0.0737

AC:

250

AN:

3390

European-Non Finnish (NFE)

AF:

0.0488

AC:

25376

AN:

519998

Other (OTH)

AF:

0.0815

AC:

2943

AN:

36130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2393

4786

7178

9571

11964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.117

AC:

17744

AN:

152252

Hom.:

1508

Cov.:

AF XY:

0.118

AC XY:

8776

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.210

AC:

8734

AN:

41530

American (AMR)

AF:

0.197

AC:

3004

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

384

AN:

3470

East Asian (EAS)

AF:

0.155

AC:

802

AN:

5182

South Asian (SAS)

AF:

0.0310

AC:

150

AN:

4832

European-Finnish (FIN)

AF:

0.0871

AC:

925

AN:

10618

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0508

AC:

3457

AN:

68028

Other (OTH)

AF:

0.111

AC:

234

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

766

1532

2297

3063

3829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0745

Hom.:

2245

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

(source)

DANN

Benign

0.51

PhyloP100

-2.0

PromoterAI

-0.0070

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