11-108219983-A-C

Variant names:

• chr11-108219983-A-C
• rs183460
• NM_002519.3:c.37+2517T>G

Variant summary

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

The NM_002519.3(NPAT):​c.37+2517T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,072 control chromosomes in the GnomAD database, including 21,913 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 0.53 (21913 hom., cov: 33)
• Consequence: NPAT NM_002519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAT	NM_002519.3	MANE Select	c.37+2517T>G		intron	N/A	NP_002510.2
	NPAT	NM_001321307.1		c.37+2517T>G		intron	N/A	NP_001308236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAT	ENST00000278612.9	TSL:1 MANE Select	c.37+2517T>G		intron	N/A	ENSP00000278612.8
	NPAT	ENST00000850623.1		c.37+2517T>G		intron	N/A	ENSP00000520908.1
	NPAT	ENST00000531384.1	TSL:5	n.37+2517T>G		intron	N/A	ENSP00000433497.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80017 AN: 151954 Hom.: 21902 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.526 AC: 80053 AN: 152072 Hom.: 21913 Cov.: 33 AF XY: 0.535 AC XY: 39792 AN XY: 74342

African (AFR) AF: 0.376 AC: 15598 AN: 41492

American (AMR) AF: 0.622 AC: 9501 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2228 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2294 AN: 5164

South Asian (SAS) AF: 0.648 AC: 3123 AN: 4822

European-Finnish (FIN) AF: 0.631 AC: 6665 AN: 10568

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38665 AN: 67968

Other (OTH) AF: 0.561 AC: 1180 AN: 2104

Alfa AF: 0.478 Hom.: 2750

Bravo AF: 0.516

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		1.3
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: rs183460; hg19: chr11-108090710;