rs228606

Variant names:

• chr11-108217120-G-T
• rs228606
• NM_002519.3:c.37+5380C>A

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+5380C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,000 control chromosomes in the GnomAD database, including 11,302 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 0.36 (11302 hom., cov: 31)
• Consequence: NPAT NM_002519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 22 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 = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAT	NM_002519.3	c.37+5380C>A		intron_variant	Intron 1 of 17	ENST00000278612.9	NP_002510.2
NPAT	NM_001321307.1	c.37+5380C>A		intron_variant	Intron 1 of 17		NP_001308236.1
NPAT	XM_011542854.3	c.37+5380C>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+5380C>A		intron_variant	Intron 1 of 17	1	NM_002519.3	ENSP00000278612.8
NPAT	ENST00000850623.1	c.37+5380C>A		intron_variant	Intron 1 of 17			ENSP00000520908.1
NPAT	ENST00000531384.1	n.37+5380C>A		intron_variant	Intron 1 of 5	5		ENSP00000433497.1
NPAT	ENST00000610253.5	n.137+5380C>A		intron_variant	Intron 1 of 12	2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54893 AN: 151882 Hom.: 11297 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.361 AC: 54908 AN: 152000 Hom.: 11302 Cov.: 31 AF XY: 0.369 AC XY: 27378 AN XY: 74284

African (AFR) AF: 0.160 AC: 6645 AN: 41480

American (AMR) AF: 0.511 AC: 7801 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2015 AN: 5162

South Asian (SAS) AF: 0.525 AC: 2523 AN: 4806

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10562

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28719 AN: 67936

Other (OTH) AF: 0.419 AC: 882 AN: 2106

Alfa AF: 0.397 Hom.: 6789

Bravo AF: 0.358

Asia WGS AF: 0.475 AC: 1650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.59
DANN	Benign	0.80
PhyloP100		-0.59
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: rs228606; hg19: chr11-108087847;