rs4758576

chr11-2952650-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAP1L4	NM_005969.4	c.1036-841C>T		intron_variant		ENST00000380542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAP1L4	ENST00000380542.9	c.1036-841C>T		intron_variant		1	NM_005969.4

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127892 AN: 152136 Hom.: 54190 Cov.: 33

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: 35 AN: 42 Hom.: 15 Cov.: 0 AF XY: 0.813 AC XY: 26 AN XY: 32

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.841 AC: 128004 AN: 152256 Hom.: 54242 Cov.: 33 AF XY: 0.841 AC XY: 62606 AN XY: 74450

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.846

Alfa AF: 0.830 Hom.: 8619

Bravo AF: 0.853

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	-0.98
Cadd	Benign	0.17
Dann	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs4758576; hg19: chr11-2973880;