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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAP1L4	NM_005969.4	MANE Select	c.14+42G>A	intron	N/A	NP_005960.1	Q99733-1
NAP1L4	NM_001369380.1		c.14+42G>A	intron	N/A	NP_001356309.1	Q99733-2
NAP1L4	NM_001369381.1		c.14+42G>A	intron	N/A	NP_001356310.1	Q99733-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAP1L4	ENST00000380542.9	TSL:1 MANE Select	c.14+42G>A	intron	N/A	ENSP00000369915.4	Q99733-1
NAP1L4	ENST00000955342.1		c.14+42G>A	intron	N/A	ENSP00000625401.1
NAP1L4	ENST00000448187.6	TSL:5	c.14+42G>A	intron	N/A	ENSP00000387783.2	C9JZI7

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over