NM_005969.4:c.14+258T>C

Variant names:

• chr11-2978949-A-G
• rs4758504
• NM_005969.4:c.14+258T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005969.4(NAP1L4):​c.14+258T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,250 control chromosomes in the GnomAD database, including 54,064 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 (54064 hom., cov: 33)
• Consequence: NAP1L4 NM_005969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L4	NM_005969.4	MANE Select	c.14+258T>C		intron	N/A	NP_005960.1
	NAP1L4	NM_001369380.1		c.14+258T>C		intron	N/A	NP_001356309.1
	NAP1L4	NM_001369381.1		c.14+258T>C		intron	N/A	NP_001356310.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L4	ENST00000380542.9	TSL:1 MANE Select	c.14+258T>C		intron	N/A	ENSP00000369915.4
	NAP1L4	ENST00000448187.6	TSL:5	c.14+258T>C		intron	N/A	ENSP00000387783.2
	NAP1L4	ENST00000703798.1		c.14+258T>C		intron	N/A	ENSP00000515483.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127662 AN: 152132 Hom.: 54010 Cov.: 33

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.839 AC: 127776 AN: 152250 Hom.: 54064 Cov.: 33 AF XY: 0.839 AC XY: 62480 AN XY: 74430

African (AFR) AF: 0.937 AC: 38950 AN: 41550

American (AMR) AF: 0.875 AC: 13383 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2839 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4709 AN: 5176

South Asian (SAS) AF: 0.884 AC: 4270 AN: 4832

European-Finnish (FIN) AF: 0.752 AC: 7956 AN: 10584

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52823 AN: 68018

Other (OTH) AF: 0.845 AC: 1787 AN: 2114

Alfa AF: 0.820 Hom.: 6633

Bravo AF: 0.852

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	-0.97
CADD	Benign	17
DANN	Benign	0.48
PhyloP100		-0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4758504; hg19: chr11-3000179;