rs10488674

chr11-2979165-C-T

Variant summary

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

The NM_005969.4(NAP1L4):c.14+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,587,334 control chromosomes in the GnomAD database, including 45,226 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 0.28 (6750 hom., cov: 33)
  • Exomes 𝑓: 0.22 (38476 hom.)
• Consequence: NAP1L4 NM_005969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAP1L4	NM_005969.4	c.14+42G>A		intron_variant		ENST00000380542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAP1L4	ENST00000380542.9	c.14+42G>A		intron_variant		1	NM_005969.4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42671 AN: 152002 Hom.: 6736 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.237

GnomAD3 exomes AF: 0.248 AC: 58914 AN: 237578 Hom.: 7886 AF XY: 0.249 AC XY: 32160 AN XY: 129072

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.206

Gnomad SAS exome AF: 0.341

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.223 AC: 320623 AN: 1435214 Hom.: 38476 Cov.: 29 AF XY: 0.227 AC XY: 161997 AN XY: 714606

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.281 AC: 42708 AN: 152120 Hom.: 6750 Cov.: 33 AF XY: 0.285 AC XY: 21201 AN XY: 74364

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.237

Alfa AF: 0.191 Hom.: 722

Bravo AF: 0.275

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.0
Dann	Benign	0.38

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: rs10488674; hg19: chr11-3000395; COSMIC: COSV65881067;