12-76083176-A-G

Variant names:

• chr12-76083176-A-G
• rs1368578
• NM_004537.7:c.-21+1391T>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.-21+1391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,058 control chromosomes in the GnomAD database, including 56,763 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 0.86 (56763 hom., cov: 29)
• Consequence: NAP1L1 NM_004537.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004537.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L1	NM_004537.7	MANE Select	c.-21+1391T>C		intron	N/A	NP_004528.1	P55209-1
	NAP1L1	NM_001330231.2		c.-21+1391T>C		intron	N/A	NP_001317160.1	P55209-1
	NAP1L1	NM_139207.5		c.-21+1391T>C		intron	N/A	NP_631946.1	P55209-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L1	ENST00000618691.5	TSL:1 MANE Select	c.-21+1391T>C		intron	N/A	ENSP00000477538.1	P55209-1
	NAP1L1	ENST00000393263.7	TSL:1	c.-21+1391T>C		intron	N/A	ENSP00000376947.3	P55209-1
	NAP1L1	ENST00000551500.1	TSL:1	n.117+1391T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.862 AC: 130906 AN: 151940 Hom.: 56696 Cov.: 29

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.862 AC: 131032 AN: 152058 Hom.: 56763 Cov.: 29 AF XY: 0.864 AC XY: 64194 AN XY: 74312

African (AFR) AF: 0.929 AC: 38516 AN: 41466

American (AMR) AF: 0.856 AC: 13077 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2971 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5168 AN: 5178

South Asian (SAS) AF: 0.933 AC: 4488 AN: 4808

European-Finnish (FIN) AF: 0.827 AC: 8733 AN: 10564

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55256 AN: 67980

Other (OTH) AF: 0.839 AC: 1767 AN: 2106

Alfa AF: 0.836 Hom.: 77208

Bravo AF: 0.867

Asia WGS AF: 0.964 AC: 3354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.54
PhyloP100		0.023
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: rs1368578; hg19: chr12-76476956;