NM_002519.3:c.556+264A>C

Variant names:

• chr11-108188842-T-G
• rs3781868
• NM_002519.3:c.556+264A>C

Variant summary

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

The NM_002519.3(NPAT):​c.556+264A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,052 control chromosomes in the GnomAD database, including 22,693 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 0.54 (22693 hom., cov: 32)
• Consequence: NPAT NM_002519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 11 publications found

Genes affected

NPAT (HGNC:7896): (nuclear protein, coactivator of histone transcription) Enables protein C-terminus binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in positive regulation of transcription by RNA polymerase II and regulation of transcription involved in G1/S transition of mitotic cell cycle. Located in Cajal body; Gemini of coiled bodies; and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPAT Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002519.3. 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
	NPAT	NM_002519.3	MANE Select	c.556+264A>C		intron	N/A	NP_002510.2
	NPAT	NM_001321307.1		c.556+264A>C		intron	N/A	NP_001308236.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAT	ENST00000278612.9	TSL:1 MANE Select	c.556+264A>C		intron	N/A	ENSP00000278612.8
	NPAT	ENST00000935790.1		c.556+264A>C		intron	N/A	ENSP00000605849.1
	NPAT	ENST00000850623.1		c.556+264A>C		intron	N/A	ENSP00000520908.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82008 AN: 151934 Hom.: 22680 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.540 AC: 82049 AN: 152052 Hom.: 22693 Cov.: 32 AF XY: 0.547 AC XY: 40675 AN XY: 74322

African (AFR) AF: 0.422 AC: 17503 AN: 41474

American (AMR) AF: 0.628 AC: 9588 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2225 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2303 AN: 5180

South Asian (SAS) AF: 0.647 AC: 3123 AN: 4824

European-Finnish (FIN) AF: 0.630 AC: 6652 AN: 10556

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38641 AN: 67964

Other (OTH) AF: 0.572 AC: 1209 AN: 2112

Alfa AF: 0.453 Hom.: 1754

Bravo AF: 0.532

Asia WGS AF: 0.576 AC: 2002 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.65
DANN	Benign	0.35
PhyloP100		-0.42
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: rs3781868; hg19: chr11-108059569;