11-2945937-C-G

Variant names:

• chr11-2945937-C-G
• rs1519
• NM_005969.4:c.*33-291G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005969.4(NAP1L4):​c.*33-291G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,044 control chromosomes in the GnomAD database, including 52,001 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 0.82 (52001 hom., cov: 30)
• Consequence: NAP1L4 NM_005969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.*33-291G>C		intron_variant	Intron 15 of 15	ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.*33-291G>C		intron_variant	Intron 15 of 15	1	NM_005969.4	ENSP00000369915.4

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125332 AN: 151926 Hom.: 51959 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.829

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.825 AC: 125432 AN: 152044 Hom.: 52001 Cov.: 30 AF XY: 0.826 AC XY: 61361 AN XY: 74316

African (AFR) AF: 0.889 AC: 36860 AN: 41482

American (AMR) AF: 0.870 AC: 13296 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2830 AN: 3470

East Asian (EAS) AF: 0.910 AC: 4698 AN: 5164

South Asian (SAS) AF: 0.887 AC: 4280 AN: 4826

European-Finnish (FIN) AF: 0.753 AC: 7927 AN: 10528

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52734 AN: 67972

Other (OTH) AF: 0.831 AC: 1755 AN: 2112

Alfa AF: 0.803 Hom.: 5737

Bravo AF: 0.835

Asia WGS AF: 0.891 AC: 3096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.45
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1519; hg19: chr11-2967167;