rs228589

Variant names:

• chr11-108222481-A-T
• rs228589
• NM_002519.3:c.37+19T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002519.3(NPAT):​c.37+19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,611,720 control chromosomes in the GnomAD database, including 257,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22720 hom., cov: 32)
  • Exomes 𝑓: 0.56 (234622 hom.)
• Consequence: NPAT NM_002519.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172
• Publications: 47 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-108222481-A-T is Benign according to our data. Variant chr11-108222481-A-T is described in ClinVar as Benign. ClinVar VariationId is 2413966.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAT	NM_002519.3	c.37+19T>A		intron_variant	Intron 1 of 17	ENST00000278612.9	NP_002510.2
NPAT	NM_001321307.1	c.37+19T>A		intron_variant	Intron 1 of 17		NP_001308236.1
NPAT	XM_011542854.3	c.37+19T>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+19T>A		intron_variant	Intron 1 of 17	1	NM_002519.3	ENSP00000278612.8
NPAT	ENST00000850623.1	c.37+19T>A		intron_variant	Intron 1 of 17			ENSP00000520908.1
NPAT	ENST00000531384.1	n.37+19T>A		intron_variant	Intron 1 of 5	5		ENSP00000433497.1
NPAT	ENST00000610253.5	n.137+19T>A		intron_variant	Intron 1 of 12	2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82055 AN: 151902 Hom.: 22707 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.571

GnomAD2 exomes AF: 0.579 AC: 142830 AN: 246702 AF XY: 0.583

Gnomad AFR exome AF: 0.416

Gnomad AMR exome AF: 0.654

Gnomad ASJ exome AF: 0.618

Gnomad EAS exome AF: 0.438

Gnomad FIN exome AF: 0.632

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.565 AC: 824564 AN: 1459700 Hom.: 234622 Cov.: 40 AF XY: 0.569 AC XY: 413100 AN XY: 725998

African (AFR) AF: 0.419 AC: 14025 AN: 33434

American (AMR) AF: 0.649 AC: 28850 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 16034 AN: 26090

East Asian (EAS) AF: 0.470 AC: 18625 AN: 39666

South Asian (SAS) AF: 0.643 AC: 55312 AN: 86020

European-Finnish (FIN) AF: 0.627 AC: 33403 AN: 53278

Middle Eastern (MID) AF: 0.721 AC: 4155 AN: 5762

European-Non Finnish (NFE) AF: 0.558 AC: 620231 AN: 1110648

Other (OTH) AF: 0.562 AC: 33929 AN: 60320

GnomAD4 genome AF: 0.540 AC: 82096 AN: 152020 Hom.: 22720 Cov.: 32 AF XY: 0.548 AC XY: 40704 AN XY: 74302

African (AFR) AF: 0.423 AC: 17531 AN: 41472

American (AMR) AF: 0.628 AC: 9603 AN: 15284

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

East Asian (EAS) AF: 0.445 AC: 2293 AN: 5152

South Asian (SAS) AF: 0.650 AC: 3127 AN: 4812

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: 38653 AN: 67962

Other (OTH) AF: 0.572 AC: 1204 AN: 2106

Alfa AF: 0.564 Hom.: 4544

Bravo AF: 0.532

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.65
PhyloP100		0.17
PromoterAI		0.089	Neutral
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: rs228589; hg19: chr11-108093208; COSMIC: COSV53716957; COSMIC: COSV53716957;