17-5420669-C-T

Position:

• chr17-5420669-C-T

Variant summary

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

The NM_001033002.4(RPAIN):​c.81+378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,768 control chromosomes in the GnomAD database, including 7,934 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 (7934 hom., cov: 31)
• Consequence: RPAIN NM_001033002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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]

RPAIN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPAIN	NM_001033002.4	c.81+378C>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.81+378C>T		intron_variant		1	NM_001033002.4	ENSP00000370606.3

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45154 AN: 151650 Hom.: 7923 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45201 AN: 151768 Hom.: 7934 Cov.: 31 AF XY: 0.311 AC XY: 23081 AN XY: 74164

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.312

Alfa AF: 0.292 Hom.: 3271

Bravo AF: 0.287

Asia WGS AF: 0.621 AC: 2154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.82

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: rs8074617; hg19: chr17-5323989;