11-2978949-A-G

Position:

• chr11-2978949-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.14+258T>C		intron_variant		ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.14+258T>C		intron_variant		1	NM_005969.4	ENSP00000369915

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

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.845

Alfa AF: 0.815 Hom.: 6284

Bravo AF: 0.852

Asia WGS AF: 0.895 AC: 3113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	17
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs4758504; hg19: chr11-3000179;