rs8070740

chr17-5428576-A-G

Variant summary

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

The NM_001033002.4(RPAIN):c.630+365A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,113,566 control chromosomes in the GnomAD database, including 46,859 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 0.27 (6943 hom., cov: 32)
  • Exomes 𝑓: 0.27 (39916 hom.)
• Consequence: RPAIN NM_001033002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPAIN	NM_001033002.4	c.630+365A>G		intron_variant		ENST00000381209.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPAIN	ENST00000381209.8	c.630+365A>G		intron_variant		1	NM_001033002.4	P1
	ENST00000575890.1	n.1583+2718T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41478 AN: 151978 Hom.: 6941 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.271 AC: 260131 AN: 961470 Hom.: 39916 Cov.: 13 AF XY: 0.276 AC XY: 127958 AN XY: 463306

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.810

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.273 AC: 41503 AN: 152096 Hom.: 6943 Cov.: 32 AF XY: 0.285 AC XY: 21191 AN XY: 74366

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.268

Alfa AF: 0.256 Hom.: 868

Bravo AF: 0.264

Asia WGS AF: 0.612 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	15
Dann	Benign	0.67

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: rs8070740; hg19: chr17-5331896;