chr11-2945063-C-G

Variant names:

• chr11-2945063-C-G
• rs8505
• NM_005969.4:c.*616G>C

Variant summary

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

The NM_005969.4(NAP1L4):​c.*616G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,564 control chromosomes in the GnomAD database, including 6,391 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 0.25 (6387 hom., cov: 32)
  • Exomes 𝑓: 0.19 (4 hom.)
• Consequence: NAP1L4 NM_005969.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.*616G>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.*616G>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_005969.4	ENSP00000369915.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37775 AN: 151350 Hom.: 6373 Cov.: 32

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.194 AC: 21 AN: 108 Hom.: 4 Cov.: 0 AF XY: 0.162 AC XY: 11 AN XY: 68

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.205 AC: 18 AN: 88

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.250 AC: 37791 AN: 151456 Hom.: 6387 Cov.: 32 AF XY: 0.254 AC XY: 18810 AN XY: 73976

African (AFR) AF: 0.0680 AC: 2807 AN: 41254

American (AMR) AF: 0.429 AC: 6538 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1139 AN: 3460

East Asian (EAS) AF: 0.672 AC: 3463 AN: 5154

South Asian (SAS) AF: 0.383 AC: 1831 AN: 4782

European-Finnish (FIN) AF: 0.210 AC: 2187 AN: 10436

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18699 AN: 67830

Other (OTH) AF: 0.294 AC: 617 AN: 2100

Alfa AF: 0.250 Hom.: 744

Bravo AF: 0.259

Asia WGS AF: 0.480 AC: 1650 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.30
DANN	Benign	0.45
PhyloP100		-2.2
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: rs8505; hg19: chr11-2966293;