rs4758621

Variant names:

• chr11-2988410-A-G
• rs4758621
• NM_005969.4:c.-18+3844T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-2988410-A-G
• chr11-2988410-A-T

Variant summary

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

The NM_005969.4(NAP1L4):​c.-18+3844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,158 control chromosomes in the GnomAD database, including 7,592 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 0.27 (7592 hom., cov: 33)
• Consequence: NAP1L4 NM_005969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.-18+3844T>C		intron_variant	Intron 1 of 15	ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.-18+3844T>C		intron_variant	Intron 1 of 15	1	NM_005969.4	ENSP00000369915.4

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41810 AN: 152040 Hom.: 7581 Cov.: 33

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.275 AC: 41827 AN: 152158 Hom.: 7592 Cov.: 33 AF XY: 0.278 AC XY: 20667 AN XY: 74382

African (AFR) AF: 0.0745 AC: 3096 AN: 41538

American (AMR) AF: 0.456 AC: 6961 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3468

East Asian (EAS) AF: 0.677 AC: 3505 AN: 5174

South Asian (SAS) AF: 0.401 AC: 1934 AN: 4818

European-Finnish (FIN) AF: 0.230 AC: 2434 AN: 10588

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21320 AN: 67990

Other (OTH) AF: 0.325 AC: 686 AN: 2108

Alfa AF: 0.306 Hom.: 3893

Bravo AF: 0.284

Asia WGS AF: 0.501 AC: 1742 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	2.1
DANN	Benign	0.65
PhyloP100		0.13
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)		0.0		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: rs4758621; hg19: chr11-3009640;