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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPAP1	NM_015540.4 link	c.541+55G>A	intron_variant	Intron 5 of 24	ENST00000304330.9	NP_056355.2	Q9BWH6-1A8K2F9
RPAP1	XM_005254297.2 link	c.541+55G>A	intron_variant	Intron 5 of 24		XP_005254354.1	Q9BWH6-1
RPAP1	XM_047432374.1 link	c.541+55G>A	intron_variant	Intron 5 of 23		XP_047288330.1
RPAP1	XM_047432375.1 link	c.541+55G>A	intron_variant	Intron 5 of 23		XP_047288331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPAP1	ENST00000304330.9 link	c.541+55G>A		intron_variant	Intron 5 of 24	1	NM_015540.4	ENSP00000306123.4		Q9BWH6-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over