chr17-5432432-C-T

Position:

• chr17-5432432-C-T

Variant summary

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

The ENST00000381209.8(RPAIN):​c.631-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,011,576 control chromosomes in the GnomAD database, including 46,661 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 0.24 (5694 hom., cov: 32)
  • Exomes 𝑓: 0.28 (40967 hom.)
• Consequence: RPAIN ENST00000381209.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPAIN	NM_001033002.4	c.631-110C>T		intron_variant		ENST00000381209.8	NP_001028174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPAIN	ENST00000381209.8	c.631-110C>T		intron_variant		1	NM_001033002.4	ENSP00000370606	P1
	ENST00000575890.1	n.445G>A		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36231 AN: 152052 Hom.: 5693 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.276 AC: 236920 AN: 859406 Hom.: 40967 Cov.: 11 AF XY: 0.281 AC XY: 126034 AN XY: 449236

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.238 AC: 36260 AN: 152170 Hom.: 5694 Cov.: 32 AF XY: 0.250 AC XY: 18614 AN XY: 74388

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.244

Alfa AF: 0.225 Hom.: 3455

Bravo AF: 0.230

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.46

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: rs8072363; hg19: chr17-5335752; COSMIC: COSV56709946; COSMIC: COSV56709946;