rs11614925

Variant names:

• chr12-76067266-A-G
• rs11614925
• NM_004537.7:c.206+105T>C

Variant summary

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

The NM_004537.7(NAP1L1):​c.206+105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 828,100 control chromosomes in the GnomAD database, including 15,025 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 0.17 (2260 hom., cov: 31)
  • Exomes 𝑓: 0.18 (12765 hom.)
• Consequence: NAP1L1 NM_004537.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• Publications: 4 publications found

Genes affected

NAP1L1 (HGNC:7637): (nucleosome assembly protein 1 like 1) This gene encodes a member of the nucleosome assembly protein (NAP) family. This protein participates in DNA replication and may play a role in modulating chromatin formation and contribute to the regulation of cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms; however, not all have been fully described. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L1	NM_004537.7	c.206+105T>C		intron_variant	Intron 4 of 14	ENST00000618691.5	NP_004528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L1	ENST00000618691.5	c.206+105T>C		intron_variant	Intron 4 of 14	1	NM_004537.7	ENSP00000477538.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25213 AN: 151972 Hom.: 2259 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.184 AC: 124142 AN: 676008 Hom.: 12765 AF XY: 0.191 AC XY: 66910 AN XY: 351050

African (AFR) AF: 0.123 AC: 2181 AN: 17770

American (AMR) AF: 0.143 AC: 4254 AN: 29798

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 3834 AN: 16470

East Asian (EAS) AF: 0.0281 AC: 989 AN: 35154

South Asian (SAS) AF: 0.314 AC: 16513 AN: 52630

European-Finnish (FIN) AF: 0.152 AC: 6092 AN: 40196

Middle Eastern (MID) AF: 0.334 AC: 784 AN: 2350

European-Non Finnish (NFE) AF: 0.185 AC: 83281 AN: 448968

Other (OTH) AF: 0.190 AC: 6214 AN: 32672

GnomAD4 genome AF: 0.166 AC: 25222 AN: 152092 Hom.: 2260 Cov.: 31 AF XY: 0.166 AC XY: 12371 AN XY: 74376

African (AFR) AF: 0.122 AC: 5050 AN: 41528

American (AMR) AF: 0.171 AC: 2619 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3466

East Asian (EAS) AF: 0.0362 AC: 188 AN: 5188

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1634 AN: 10590

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12710 AN: 67904

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.181 Hom.: 6842

Bravo AF: 0.163

Asia WGS AF: 0.168 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.9
DANN	Benign	0.43
PhyloP100		0.19
PromoterAI		-0.0031	Neutral
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: rs11614925; hg19: chr12-76461046;