11-108219983-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002519.3(NPAT):​c.37+2517T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,000 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAT	NM_002519.3	c.37+2517T>A		intron_variant	Intron 1 of 17	ENST00000278612.9	NP_002510.2
NPAT	NM_001321307.1	c.37+2517T>A		intron_variant	Intron 1 of 17		NP_001308236.1
NPAT	XM_011542854.3	c.37+2517T>A		intron_variant	Intron 1 of 17		XP_011541156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAT	ENST00000278612.9	c.37+2517T>A		intron_variant	Intron 1 of 17	1	NM_002519.3	ENSP00000278612.8
NPAT	ENST00000850623.1	c.37+2517T>A		intron_variant	Intron 1 of 17			ENSP00000520908.1
NPAT	ENST00000531384.1	n.37+2517T>A		intron_variant	Intron 1 of 5	5		ENSP00000433497.1
NPAT	ENST00000610253.5	n.137+2517T>A		intron_variant	Intron 1 of 12	2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152000 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152000 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74236

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 2750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.9
DANN	Benign	0.66
PhyloP100		1.3

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;