Genetic Variant NAP1L4:c.*616G>C (chr11-2945063-C-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_005969.4(NAP1L4):c.*616G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,564 control chromosomes in the GnomAD database, including 6,391 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 0.25 ( 6387 hom., cov: 32)

Exomes 𝑓: 0.19 ( 4 hom. )

Consequence

NAP1L4
NM_005969.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.21

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 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.*616G>C	3_prime_UTR	Exon 16 of 16	NP_005960.1	Q99733-1
NAP1L4	NM_001369380.1		c.*545G>C	3_prime_UTR	Exon 15 of 15	NP_001356309.1	Q99733-2
NAP1L4	NM_001369381.1		c.*545G>C	3_prime_UTR	Exon 16 of 16	NP_001356310.1	Q99733-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAP1L4	ENST00000380542.9	TSL:1 MANE Select	c.*616G>C	3_prime_UTR	Exon 16 of 16	ENSP00000369915.4	Q99733-1
NAP1L4	ENST00000955342.1		c.*616G>C	3_prime_UTR	Exon 17 of 17	ENSP00000625401.1
NAP1L4	ENST00000448187.6	TSL:5	c.*545G>C	3_prime_UTR	Exon 15 of 15	ENSP00000387783.2	C9JZI7

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37775

AN:

151350

Hom.:

6373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0682

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.194

AC:

AN:

108

Hom.:

Cov.:

AF XY:

0.162

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.250

AC:

37791

AN:

151456

Hom.:

6387

Cov.:

AF XY:

0.254

AC XY:

18810

AN XY:

73976

show subpopulations

African (AFR)

AF:

0.0680

AC:

2807

AN:

41254

American (AMR)

AF:

0.429

AC:

6538

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1139

AN:

3460

East Asian (EAS)

AF:

0.672

AC:

3463

AN:

5154

South Asian (SAS)

AF:

0.383

AC:

1831

AN:

4782

European-Finnish (FIN)

AF:

0.210

AC:

2187

AN:

10436

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.276

AC:

18699

AN:

67830

Other (OTH)

AF:

0.294

AC:

617

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1287

2574

3860

5147

6434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.250

Hom.:

744

Bravo

AF:

0.259

Asia WGS

AF:

0.480

AC:

1650

AN:

3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.30

(source)

DANN

Benign

0.45

PhyloP100

-2.2

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