17-5427639-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033002.4(RPAIN):​c.490-432C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 158,020 control chromosomes in the GnomAD database, including 7,308 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 (6810 hom., cov: 30)
  • Exomes 𝑓: 0.32 (498 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033002.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAIN	NM_001033002.4	MANE Select	c.490-432C>G		intron	N/A	NP_001028174.2	Q86UA6-1
	RPAIN	NM_001160243.2		c.490-432C>G		intron	N/A	NP_001153715.1	Q86UA6-8
	RPAIN	NM_001160244.2		c.489+1340C>G		intron	N/A	NP_001153716.1	Q86UA6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAIN	ENST00000381209.8	TSL:1 MANE Select	c.490-432C>G		intron	N/A	ENSP00000370606.3	Q86UA6-1
	RPAIN	ENST00000381208.9	TSL:1	c.489+1340C>G		intron	N/A	ENSP00000370605.5	Q86UA6-2
	RPAIN	ENST00000536255.6	TSL:1	c.313+4810C>G		intron	N/A	ENSP00000439939.2	Q86UA6-6

Frequencies

GnomAD3 genomes AF: 0.272 AC: 40989 AN: 150468 Hom.: 6808 Cov.: 30

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.319 AC: 2373 AN: 7434 Hom.: 498 Cov.: 0 AF XY: 0.331 AC XY: 1304 AN XY: 3938

African (AFR) AF: 0.121 AC: 8 AN: 66

American (AMR) AF: 0.374 AC: 591 AN: 1582

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 22 AN: 96

East Asian (EAS) AF: 0.828 AC: 207 AN: 250

South Asian (SAS) AF: 0.491 AC: 492 AN: 1002

European-Finnish (FIN) AF: 0.314 AC: 22 AN: 70

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.233 AC: 948 AN: 4068

Other (OTH) AF: 0.277 AC: 83 AN: 300

GnomAD4 genome AF: 0.272 AC: 41014 AN: 150586 Hom.: 6810 Cov.: 30 AF XY: 0.284 AC XY: 20866 AN XY: 73458

African (AFR) AF: 0.177 AC: 7216 AN: 40810

American (AMR) AF: 0.317 AC: 4791 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3464

East Asian (EAS) AF: 0.818 AC: 4191 AN: 5124

South Asian (SAS) AF: 0.511 AC: 2430 AN: 4754

European-Finnish (FIN) AF: 0.371 AC: 3793 AN: 10216

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16906 AN: 67816

Other (OTH) AF: 0.267 AC: 560 AN: 2094

Alfa AF: 0.143 Hom.: 289

Bravo AF: 0.264

Asia WGS AF: 0.604 AC: 2093 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.54
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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;