chr17-5427639-C-A

Variant names:

• chr17-5427639-C-A
• rs4790772
• NM_001033002.4:c.490-432C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001033002.4(RPAIN):​c.490-432C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000664 in 150,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPAIN NM_001033002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 4 publications found

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]

ENSG00000263272 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPAIN	NM_001033002.4	c.490-432C>A		intron_variant	Intron 5 of 6	ENST00000381209.8	NP_001028174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPAIN	ENST00000381209.8	c.490-432C>A		intron_variant	Intron 5 of 6	1	NM_001033002.4	ENSP00000370606.3

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150556 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 7450 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3946

African (AFR) AF: 0.00 AC: 0 AN: 66

American (AMR) AF: 0.00 AC: 0 AN: 1584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 96

East Asian (EAS) AF: 0.00 AC: 0 AN: 252

South Asian (SAS) AF: 0.00 AC: 0 AN: 1008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 70

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4074

Other (OTH) AF: 0.00 AC: 0 AN: 300

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150556 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73372

African (AFR) AF: 0.00 AC: 0 AN: 40706

American (AMR) AF: 0.00 AC: 0 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67854

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.36
PhyloP100		-0.47

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: rs4790772; hg19: chr17-5330959;