dbSNP rs10488674: NAP1L4:c.14+42G>A (chr11-2979165-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_005969.4(NAP1L4):c.14+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,587,334 control chromosomes in the GnomAD database, including 45,226 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 0.28 ( 6750 hom., cov: 33)

Exomes 𝑓: 0.22 ( 38476 hom. )

Consequence

NAP1L4
NM_005969.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.928

Publications

11 publications found

Variant links:

Genes affected

NAP1L4 (HGNC:7640): (nucleosome assembly protein 1 like 4) This gene encodes a member of the nucleosome assembly protein (NAP) family which can interact with both core and linker histones. It can shuttle between the cytoplasm and nucleus, suggesting a role as a histone chaperone. This gene is one of several located near the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. [provided by RefSeq, Jul 2008]

NAP1L4 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4 link	c.14+42G>A		intron_variant	Intron 2 of 15	ENST00000380542.9	NP_005960.1	Q99733-1A0A024RCC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9 link	c.14+42G>A		intron_variant	Intron 2 of 15	1	NM_005969.4	ENSP00000369915.4		Q99733-1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42671

AN:

152002

Hom.:

6736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.237

GnomAD2 exomes

AF:

0.248

AC:

58914

AN:

237578

AF XY:

0.249

show subpopulations

Gnomad AFR exome

AF:

0.431

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.223

AC:

320623

AN:

1435214

Hom.:

38476

Cov.:

AF XY:

0.227

AC XY:

161997

AN XY:

714606

show subpopulations

African (AFR)

AF:

0.423

AC:

13650

AN:

32254

American (AMR)

AF:

0.197

AC:

8224

AN:

41682

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

4952

AN:

25648

East Asian (EAS)

AF:

0.230

AC:

9038

AN:

39282

South Asian (SAS)

AF:

0.334

AC:

27730

AN:

82960

European-Finnish (FIN)

AF:

0.328

AC:

17448

AN:

53268

Middle Eastern (MID)

AF:

0.212

AC:

1206

AN:

5688

European-Non Finnish (NFE)

AF:

0.205

AC:

224735

AN:

1094994

Other (OTH)

AF:

0.229

AC:

13640

AN:

59438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

10402

20804

31206

41608

52010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7818

15636

23454

31272

39090

<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:

0.281

AC:

42708

AN:

152120

Hom.:

6750

Cov.:

AF XY:

0.285

AC XY:

21201

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.421

AC:

17462

AN:

41464

American (AMR)

AF:

0.213

AC:

3248

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3472

East Asian (EAS)

AF:

0.205

AC:

1064

AN:

5190

South Asian (SAS)

AF:

0.337

AC:

1628

AN:

4828

European-Finnish (FIN)

AF:

0.342

AC:

3618

AN:

10566

Middle Eastern (MID)

AF:

0.229

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.211

AC:

14337

AN:

68008

Other (OTH)

AF:

0.237

AC:

499

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1478

2956

4433

5911

7389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.197

Hom.:

795

Bravo

AF:

0.275

Asia WGS

AF:

0.277

AC:

964

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

(source)

DANN

Benign

0.38

PhyloP100

-0.93

Mutation Taster

=100/0

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