rs11024758

Variant names:

• chr11-2960552-C-T
• rs11024758
• NM_005969.4:c.607-643G>A

Variant summary

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

The NM_005969.4(NAP1L4):​c.607-643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,148 control chromosomes in the GnomAD database, including 1,554 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 0.14 (1554 hom., cov: 32)
• Consequence: NAP1L4 NM_005969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.607-643G>A		intron_variant	Intron 8 of 15	ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.607-643G>A		intron_variant	Intron 8 of 15	1	NM_005969.4	ENSP00000369915.4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21166 AN: 152030 Hom.: 1555 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.139 AC: 21162 AN: 152148 Hom.: 1554 Cov.: 32 AF XY: 0.134 AC XY: 9939 AN XY: 74376

African (AFR) AF: 0.111 AC: 4628 AN: 41518

American (AMR) AF: 0.131 AC: 1995 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.0242 AC: 125 AN: 5170

South Asian (SAS) AF: 0.0852 AC: 411 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1150 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11666 AN: 67992

Other (OTH) AF: 0.155 AC: 327 AN: 2108

Alfa AF: 0.160 Hom.: 473

Bravo AF: 0.138

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.58
PhyloP100		-0.12
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: rs11024758; hg19: chr11-2981782;