dbSNP rs2297381: RPAP1:c.541+55G>A (chr15-41535457-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015540.4(RPAP1):c.541+55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,542,560 control chromosomes in the GnomAD database, including 199,876 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 0.42 ( 14812 hom., cov: 32)

Exomes 𝑓: 0.51 ( 185064 hom. )

Consequence

RPAP1
NM_015540.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.409

Publications

26 publications found

Variant links:

Genes affected

RPAP1 (HGNC:24567): (RNA polymerase II associated protein 1) This protein forms part of the RNA polymerase II (RNAPII) enzyme complex and may recruit RNAPII to chromatin through its interaction with acetylated histones. [provided by RefSeq, Jul 2012]

RPAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015540.4. 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
	RPAP1	NM_015540.4	MANE Select	c.541+55G>A		intron	N/A	NP_056355.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPAP1	ENST00000304330.9	TSL:1 MANE Select	c.541+55G>A	intron	N/A	ENSP00000306123.4	Q9BWH6-1
RPAP1	ENST00000562303.5	TSL:1	n.541+55G>A	intron	N/A	ENSP00000455363.1	Q9BWH6-2
RPAP1	ENST00000867493.1		c.541+55G>A	intron	N/A	ENSP00000537552.1

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63708

AN:

151910

Hom.:

14814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.550

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.457

GnomAD4 exome

AF:

0.512

AC:

712551

AN:

1390532

Hom.:

185064

AF XY:

0.513

AC XY:

352758

AN XY:

687392

show subpopulations

African (AFR)

AF:

0.191

AC:

5757

AN:

30154

American (AMR)

AF:

0.399

AC:

12073

AN:

30254

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

10737

AN:

22048

East Asian (EAS)

AF:

0.543

AC:

20772

AN:

38284

South Asian (SAS)

AF:

0.529

AC:

39686

AN:

74972

European-Finnish (FIN)

AF:

0.477

AC:

24508

AN:

51328

Middle Eastern (MID)

AF:

0.564

AC:

2225

AN:

3948

European-Non Finnish (NFE)

AF:

0.526

AC:

568775

AN:

1082276

Other (OTH)

AF:

0.489

AC:

28018

AN:

57268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

16069

32139

48208

64278

80347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16564

33128

49692

66256

82820

<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:

0.419

AC:

63717

AN:

152028

Hom.:

14812

Cov.:

AF XY:

0.422

AC XY:

31399

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.205

AC:

8511

AN:

41480

American (AMR)

AF:

0.427

AC:

6517

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

1654

AN:

3464

East Asian (EAS)

AF:

0.488

AC:

2519

AN:

5158

South Asian (SAS)

AF:

0.528

AC:

2544

AN:

4820

European-Finnish (FIN)

AF:

0.477

AC:

5047

AN:

10570

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35302

AN:

67954

Other (OTH)

AF:

0.461

AC:

974

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1760

3519

5279

7038

8798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.483

Hom.:

35175

Bravo

AF:

0.405

Asia WGS

AF:

0.468

AC:

1628

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.5

(source)

DANN

Benign

0.51

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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