11-2978277-G-T

Position:

• chr11-2978277-G-T

Variant summary

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

The NM_005969.4(NAP1L4):​c.73+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,611,538 control chromosomes in the GnomAD database, including 85,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7554 hom., cov: 32)
  • Exomes 𝑓: 0.31 (77912 hom.)
• Consequence: NAP1L4 NM_005969.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001851
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660

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 (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.73+7C>A		splice_region_variant, intron_variant		ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.73+7C>A		splice_region_variant, intron_variant		1	NM_005969.4	ENSP00000369915.4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43860 AN: 151982 Hom.: 7541 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.321

GnomAD3 exomes AF: 0.363 AC: 90313 AN: 248848 Hom.: 19040 AF XY: 0.357 AC XY: 48176 AN XY: 135042

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.677

Gnomad SAS exome AF: 0.380

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.314 AC: 458416 AN: 1459438 Hom.: 77912 Cov.: 32 AF XY: 0.315 AC XY: 228988 AN XY: 726108

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.289 AC: 43903 AN: 152100 Hom.: 7554 Cov.: 32 AF XY: 0.292 AC XY: 21710 AN XY: 74376

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.327

Alfa AF: 0.298 Hom.: 9000

Bravo AF: 0.302

Asia WGS AF: 0.505 AC: 1754 AN: 3478

EpiCase AF: 0.305

EpiControl AF: 0.315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
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: rs3814964; hg19: chr11-2999507; COSMIC: COSV65882641;