rs2297381

Positions:

• chr15-41535457-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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]

ACMG classification

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
RPAP1	NM_015540.4	c.541+55G>A		intron_variant		ENST00000304330.9
RPAP1	XM_005254297.2	c.541+55G>A		intron_variant
RPAP1	XM_047432374.1	c.541+55G>A		intron_variant
RPAP1	XM_047432375.1	c.541+55G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPAP1	ENST00000304330.9	c.541+55G>A		intron_variant		1	NM_015540.4	P1
RPAP1	ENST00000562303.5	c.541+55G>A		intron_variant, NMD_transcript_variant		1
RPAP1	ENST00000561603.5	c.541+55G>A		intron_variant		5
RPAP1	ENST00000563293.1	n.368+55G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63708 AN: 151910 Hom.: 14814 Cov.: 32

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

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

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

Other links and lift over

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