chr15-41521081-C-T

Variant names:

• chr15-41521081-C-T
• rs3743031
• NM_015540.4:c.3105G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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	c.3105G>A	p.Arg1035Arg	synonymous_variant	Exon 22 of 25	ENST00000304330.9	NP_056355.2
RPAP1	XM_005254297.2	c.3105G>A	p.Arg1035Arg	synonymous_variant	Exon 22 of 25		XP_005254354.1
RPAP1	XM_047432374.1	c.2925G>A	p.Arg975Arg	synonymous_variant	Exon 21 of 24		XP_047288330.1
RPAP1	XM_047432375.1	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	Appris	UniProt
RPAP1	ENST00000304330.9	c.3105G>A	p.Arg1035Arg	synonymous_variant	Exon 22 of 25	1	NM_015540.4	ENSP00000306123.4
RPAP1	ENST00000562303.5	n.3105G>A		non_coding_transcript_exon_variant	Exon 22 of 24	1		ENSP00000455363.1
RPAP1	ENST00000565167.1	n.121G>A		non_coding_transcript_exon_variant	Exon 2 of 4	1
RPAP1	ENST00000561603.5	c.3038+657G>A		intron_variant	Intron 21 of 23	5		ENSP00000456207.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51789 AN: 151908 Hom.: 9806 Cov.: 32

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

GnomAD2 exomes AF: 0.378 AC: 70251 AN: 185632 AF XY: 0.385

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 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.: 38 AF XY: 0.416 AC XY: 281704 AN XY: 676670

African (AFR) AF: 0.158 AC: 4881 AN: 30914

American (AMR) AF: 0.341 AC: 10871 AN: 31886

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 8169 AN: 20576

East Asian (EAS) AF: 0.350 AC: 13625 AN: 38978

South Asian (SAS) AF: 0.393 AC: 28406 AN: 72252

European-Finnish (FIN) AF: 0.424 AC: 21064 AN: 49632

Middle Eastern (MID) AF: 0.471 AC: 2518 AN: 5350

European-Non Finnish (NFE) AF: 0.431 AC: 462005 AN: 1072020

Other (OTH) AF: 0.396 AC: 22452 AN: 56726

GnomAD4 genome AF: 0.341 AC: 51809 AN: 152026 Hom.: 9812 Cov.: 32 AF XY: 0.345 AC XY: 25619 AN XY: 74332

African (AFR) AF: 0.167 AC: 6947 AN: 41492

American (AMR) AF: 0.364 AC: 5558 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1397 AN: 3472

East Asian (EAS) AF: 0.314 AC: 1616 AN: 5144

South Asian (SAS) AF: 0.399 AC: 1920 AN: 4816

European-Finnish (FIN) AF: 0.422 AC: 4458 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28622 AN: 67950

Other (OTH) AF: 0.375 AC: 791 AN: 2110

Alfa AF: 0.381 Hom.: 29766

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
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3743031; hg19: chr15-41813279; COSMIC: COSV58537604; COSMIC: COSV58537604;