dbSNP rs228589: NPAT:c.37+19T>A (chr11-108222481-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.172

Publications

47 publications found

Variant links:

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

NPAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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.37+19T>A		intron	N/A	NP_002510.2	Q14207
	NPAT	NM_001321307.1		c.37+19T>A		intron	N/A	NP_001308236.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPAT	ENST00000278612.9	TSL:1 MANE Select	c.37+19T>A	intron	N/A	ENSP00000278612.8	Q14207
NPAT	ENST00000935790.1		c.37+19T>A	intron	N/A	ENSP00000605849.1
NPAT	ENST00000850623.1		c.37+19T>A	intron	N/A	ENSP00000520908.1	Q14207

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82055

AN:

151902

Hom.:

22707

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.569

AC XY:

413100

AN XY:

725998

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18571

37142

55713

74284

92855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17320

34640

51960

69280

86600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.540

AC:

82096

AN:

152020

Hom.:

22720

Cov.:

AF XY:

0.548

AC XY:

40704

AN XY:

74302

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1921

3842

5764

7685

9606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.564

Hom.:

4544

Bravo

AF:

0.532

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.8

(source)

DANN

Benign

0.65

PhyloP100

0.17

PromoterAI

0.089

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over