Genetic Variant NM_001033002.4:c.490-432C>G (chr17-5427639-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.474

Publications

4 publications found

Variant links:

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 links:

ENSG00000263272 (HGNC:):

ENSG00000263272 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPAIN	NM_001033002.4 link	c.490-432C>G		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 link	c.490-432C>G		intron_variant	Intron 5 of 6	1	NM_001033002.4	ENSP00000370606.3		Q86UA6-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

40989

AN:

150468

Hom.:

6808

Cov.:

show subpopulations

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.:

AF XY:

0.331

AC XY:

1304

AN XY:

3938

show subpopulations

African (AFR)

AF:

0.121

AC:

AN:

American (AMR)

AF:

0.374

AC:

591

AN:

1582

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

AN:

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:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.233

AC:

948

AN:

4068

Other (OTH)

AF:

0.277

AC:

AN:

300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.272

AC:

41014

AN:

150586

Hom.:

6810

Cov.:

AF XY:

0.284

AC XY:

20866

AN XY:

73458

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.249

AC:

16906

AN:

67816

Other (OTH)

AF:

0.267

AC:

560

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1324

2648

3972

5296

6620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.65

(source)

DANN

Benign

0.54

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over