11-2978277-G-T

Variant names:

• chr11-2978277-G-T
• rs3814964
• NM_005969.4:c.73+7C>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.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
• Publications: 20 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 = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.73+7C>A		splice_region_variant, intron_variant	Intron 3 of 15	ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.73+7C>A		splice_region_variant, intron_variant	Intron 3 of 15	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

GnomAD2 exomes AF: 0.363 AC: 90313 AN: 248848 AF XY: 0.357

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 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

African (AFR) AF: 0.151 AC: 5049 AN: 33444

American (AMR) AF: 0.562 AC: 25112 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 9120 AN: 26112

East Asian (EAS) AF: 0.668 AC: 26483 AN: 39628

South Asian (SAS) AF: 0.380 AC: 32728 AN: 86166

European-Finnish (FIN) AF: 0.229 AC: 12243 AN: 53378

Middle Eastern (MID) AF: 0.341 AC: 1964 AN: 5764

European-Non Finnish (NFE) AF: 0.294 AC: 326041 AN: 1110006

Other (OTH) AF: 0.326 AC: 19676 AN: 60286

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

African (AFR) AF: 0.159 AC: 6588 AN: 41476

American (AMR) AF: 0.449 AC: 6863 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3472

East Asian (EAS) AF: 0.675 AC: 3495 AN: 5174

South Asian (SAS) AF: 0.398 AC: 1917 AN: 4816

European-Finnish (FIN) AF: 0.224 AC: 2378 AN: 10596

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20145 AN: 67974

Other (OTH) AF: 0.327 AC: 691 AN: 2114

Alfa AF: 0.297 Hom.: 11254

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
PhyloP100		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3814964; hg19: chr11-2999507; COSMIC: COSV65882641;