Genetic Variant NPIPB4:p.Glu306Lys (chr16-21837471-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001384980.1(NPIPB4):c.916G>A(p.Glu306Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 7 hom., cov: 7)

Exomes 𝑓: 0.0024 ( 183 hom. )

Consequence

NPIPB4
NM_001384980.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.260

Publications

1 publications found

Variant links:

Genes affected

NPIPB4 (HGNC:41985): (nuclear pore complex interacting protein family member B4) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPB4 links:

ENSG00000302351 (HGNC:):

ENSG00000302351 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00807029).

BP6

Variant 16-21837471-C-T is Benign according to our data. Variant chr16-21837471-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3239057.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384980.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPIPB4	NM_001384980.1	MANE Select	c.916G>A	p.Glu306Lys	missense	Exon 8 of 8	NP_001371909.1	C9JB18
NPIPB4	NM_001310148.2		c.916G>A	p.Glu306Lys	missense	Exon 8 of 8	NP_001297077.1	C9JB18
NPIPB4	NM_001384979.1		c.916G>A	p.Glu306Lys	missense	Exon 8 of 8	NP_001371908.1	C9JB18

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPIPB4	ENST00000682606.1	MANE Select	c.916G>A	p.Glu306Lys	missense	Exon 8 of 8	ENSP00000507812.1	C9JB18
NPIPB4	ENST00000341400.12	TSL:2	c.916G>A	p.Glu306Lys	missense	Exon 7 of 7	ENSP00000339196.8	C9JB18
NPIPB4	ENST00000956755.1		c.916G>A	p.Glu306Lys	missense	Exon 9 of 9	ENSP00000626814.1

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

178

AN:

51432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000387

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0227

Gnomad NFE

AF:

0.00272

Gnomad OTH

AF:

0.00429

GnomAD2 exomes

AF:

0.00126

AC:

105

AN:

83536

AF XY:

0.00124

show subpopulations

Gnomad AFR exome

AF:

0.000640

Gnomad AMR exome

AF:

0.000218

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00332

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.000730

GnomAD4 exome

AF:

0.00243

AC:

1490

AN:

613486

Hom.:

183

Cov.:

AF XY:

0.00220

AC XY:

718

AN XY:

327044

show subpopulations

African (AFR)

AF:

0.000379

AC:

AN:

13180

American (AMR)

AF:

0.000264

AC:

AN:

30254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18084

East Asian (EAS)

AF:

0.0000339

AC:

AN:

29466

South Asian (SAS)

AF:

0.000170

AC:

AN:

52810

European-Finnish (FIN)

AF:

0.0211

AC:

716

AN:

33990

Middle Eastern (MID)

AF:

0.000443

AC:

AN:

2258

European-Non Finnish (NFE)

AF:

0.00169

AC:

681

AN:

402216

Other (OTH)

AF:

0.00221

AC:

AN:

31228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00346

AC:

178

AN:

51440

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

AN XY:

24228

show subpopulations

African (AFR)

AF:

0.000982

AC:

AN:

4072

American (AMR)

AF:

0.000387

AC:

AN:

5168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1560

East Asian (EAS)

AF:

0.00

AC:

AN:

592

South Asian (SAS)

AF:

0.00

AC:

AN:

612

European-Finnish (FIN)

AF:

0.0183

AC:

AN:

4090

Middle Eastern (MID)

AF:

0.0227

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00272

AC:

AN:

34178

Other (OTH)

AF:

0.00427

AC:

AN:

702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00141

Hom.:

ExAC

AF:

0.000396

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.00092

LIST_S2

Benign

0.67

M_CAP

Benign

0.028

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.92

PhyloP100

0.26

PROVEAN

Benign

-1.4

REVEL

Benign

0.082

Sift

Benign

0.17

Sift4G

Benign

0.39

Polyphen

0.99

Vest4

0.082

MVP

0.12

ClinPred

0.79

Varity_R

0.12

gMVP

0.072

Mutation Taster

=95/5

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over