Genetic Variant RPAP1:p.Arg1035Arg (chr15-41521081-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015540.4(RPAP1):c.3105G>A(p.Arg1035Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,530,360 control chromosomes in the GnomAD database, including 131,171 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 0.34 ( 9812 hom., cov: 32)

Exomes 𝑓: 0.42 ( 121359 hom. )

Consequence

RPAP1
NM_015540.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.621

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=0.621 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPAP1	NM_015540.4 link	c.3105G>A	p.Arg1035Arg	synonymous_variant	Exon 22 of 25	ENST00000304330.9	NP_056355.2	Q9BWH6-1A8K2F9
RPAP1	XM_005254297.2 link	c.3105G>A	p.Arg1035Arg	synonymous_variant	Exon 22 of 25		XP_005254354.1	Q9BWH6-1
RPAP1	XM_047432374.1 link	c.2925G>A	p.Arg975Arg	synonymous_variant	Exon 21 of 24		XP_047288330.1
RPAP1	XM_047432375.1 link	c.2925G>A	p.Arg975Arg	synonymous_variant	Exon 21 of 24		XP_047288331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RPAP1	ENST00000304330.9 link	c.3105G>A	p.Arg1035Arg	synonymous_variant	Exon 22 of 25	1	NM_015540.4	ENSP00000306123.4	Q9BWH6-1
RPAP1	ENST00000562303.5 link	n.3105G>A		non_coding_transcript_exon_variant	Exon 22 of 24	1		ENSP00000455363.1	Q9BWH6-2
RPAP1	ENST00000565167.1 link	n.121G>A		non_coding_transcript_exon_variant	Exon 2 of 4	1
RPAP1	ENST00000561603.5 link	c.3038+657G>A		intron_variant	Intron 21 of 23	5		ENSP00000456207.1	H3BRE8

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51789

AN:

151908

Hom.:

9806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.370

GnomAD3 exomes

AF:

0.378

AC:

70251

AN:

185632

Hom.:

13657

AF XY:

0.385

AC XY:

37855

AN XY:

98318

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.403

Gnomad EAS exome

AF:

0.290

Gnomad SAS exome

AF:

0.397

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.416

AC:

573991

AN:

1378334

Hom.:

121359

Cov.:

AF XY:

0.416

AC XY:

281704

AN XY:

676670

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.431

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.341

AC:

51809

AN:

152026

Hom.:

9812

Cov.:

AF XY:

0.345

AC XY:

25619

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.396

Hom.:

21286

Bravo

AF:

0.329

Asia WGS

AF:

0.338

AC:

1174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.5

DANN

Benign

0.48

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over