rs2297381

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.409
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 HGVSp Effect #exon/exons MANE UniProt
RPAP1NM_015540.4 linkuse as main transcriptc.541+55G>A intron_variant ENST00000304330.9
RPAP1XM_005254297.2 linkuse as main transcriptc.541+55G>A intron_variant
RPAP1XM_047432374.1 linkuse as main transcriptc.541+55G>A intron_variant
RPAP1XM_047432375.1 linkuse as main transcriptc.541+55G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPAP1ENST00000304330.9 linkuse as main transcriptc.541+55G>A intron_variant 1 NM_015540.4 P1Q9BWH6-1
RPAP1ENST00000562303.5 linkuse as main transcriptc.541+55G>A intron_variant, NMD_transcript_variant 1 Q9BWH6-2
RPAP1ENST00000561603.5 linkuse as main transcriptc.541+55G>A intron_variant 5
RPAP1ENST00000563293.1 linkuse as main transcriptn.368+55G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.419
AC:
63708
AN:
151910
Hom.:
14814
Cov.:
32
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
Gnomad4 AFR exome
AF:
0.191
Gnomad4 AMR exome
AF:
0.399
Gnomad4 ASJ exome
AF:
0.487
Gnomad4 EAS exome
AF:
0.543
Gnomad4 SAS exome
AF:
0.529
Gnomad4 FIN exome
AF:
0.477
Gnomad4 NFE exome
AF:
0.526
Gnomad4 OTH exome
AF:
0.489
GnomAD4 genome
AF:
0.419
AC:
63717
AN:
152028
Hom.:
14812
Cov.:
32
AF XY:
0.422
AC XY:
31399
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.205
Gnomad4 AMR
AF:
0.427
Gnomad4 ASJ
AF:
0.477
Gnomad4 EAS
AF:
0.488
Gnomad4 SAS
AF:
0.528
Gnomad4 FIN
AF:
0.477
Gnomad4 NFE
AF:
0.519
Gnomad4 OTH
AF:
0.461
Alfa
AF:
0.493
Hom.:
26555
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
DANN
Benign
0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2297381; hg19: chr15-41827655; COSMIC: COSV58538820; COSMIC: COSV58538820; API