dbSNP rs4758576: NAP1L4:c.1036-841C>T (chr11-2952650-G-A) – 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.1036-841C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,298 control chromosomes in the GnomAD database, including 54,257 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 0.84 ( 54242 hom., cov: 33)

Exomes 𝑓: 0.83 ( 15 hom. )

Consequence

NAP1L4
NM_005969.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

6 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:

Genome browser will be placed here

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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 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
NAP1L4	NM_005969.4	MANE Select	c.1036-841C>T	intron	N/A	NP_005960.1
NAP1L4	NM_001369380.1		c.1036-841C>T	intron	N/A	NP_001356309.1
NAP1L4	NM_001369381.1		c.1036-841C>T	intron	N/A	NP_001356310.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAP1L4	ENST00000380542.9	TSL:1 MANE Select	c.1036-841C>T	intron	N/A	ENSP00000369915.4
NAP1L4	ENST00000469805.5	TSL:3	n.120C>T	non_coding_transcript_exon	Exon 1 of 4
NAP1L4	ENST00000448187.6	TSL:5	c.1072-841C>T	intron	N/A	ENSP00000387783.2

Frequencies

GnomAD3 genomes

AF:

0.841

AC:

127892

AN:

152136

Hom.:

54190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.939

Gnomad AMI

AF:

0.883

Gnomad AMR

AF:

0.875

Gnomad ASJ

AF:

0.818

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.779

Gnomad OTH

AF:

0.844

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.813

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.808

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

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:

0.841

AC:

128004

AN:

152256

Hom.:

54242

Cov.:

AF XY:

0.841

AC XY:

62606

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.939

AC:

38998

AN:

41552

American (AMR)

AF:

0.876

AC:

13392

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.818

AC:

2839

AN:

3472

East Asian (EAS)

AF:

0.910

AC:

4711

AN:

5178

South Asian (SAS)

AF:

0.887

AC:

4273

AN:

4820

European-Finnish (FIN)

AF:

0.752

AC:

7973

AN:

10600

Middle Eastern (MID)

AF:

0.861

AC:

253

AN:

294

European-Non Finnish (NFE)

AF:

0.779

AC:

52972

AN:

68018

Other (OTH)

AF:

0.846

AC:

1788

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1023

2045

3068

4090

5113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.832

Hom.:

17650

Bravo

AF:

0.853

Asia WGS

AF:

0.895

AC:

3113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.17

(source)

DANN

Benign

0.55

PhyloP100

-1.9

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