rs4790770

Positions:

• chr17-5421573-A-C

Variant summary

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

The NM_001033002.4(RPAIN):​c.252+107A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 948,114 control chromosomes in the GnomAD database, including 53,583 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 0.30 (7977 hom., cov: 31)
  • Exomes 𝑓: 0.31 (45606 hom.)
• Consequence: RPAIN NM_001033002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

Genes affected

RPAIN (HGNC:28641): (RPA interacting protein) Predicted to enable metal ion binding activity. Acts upstream of or within several processes, including DNA metabolic process; protein import into nucleus; and response to UV. Located in PML body; cytoplasm; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPAIN	NM_001033002.4	c.252+107A>C		intron_variant		ENST00000381209.8	NP_001028174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPAIN	ENST00000381209.8	c.252+107A>C		intron_variant		1	NM_001033002.4	ENSP00000370606	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45204 AN: 151492 Hom.: 7966 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.310 AC: 247132 AN: 796504 Hom.: 45606 Cov.: 10 AF XY: 0.317 AC XY: 128211 AN XY: 403828

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.298 AC: 45250 AN: 151610 Hom.: 7977 Cov.: 31 AF XY: 0.312 AC XY: 23090 AN XY: 74052

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.313

Alfa AF: 0.292 Hom.: 3273

Bravo AF: 0.288

Asia WGS AF: 0.623 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs4790770; hg19: chr17-5324893;