Genetic Variant RPAIN:c.630+365A>G (chr17-5428576-A-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.630+365A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,113,566 control chromosomes in the GnomAD database, including 46,859 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 ( 6943 hom., cov: 32)

Exomes 𝑓: 0.27 ( 39916 hom. )

Consequence

RPAIN
NM_001033002.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Publications

18 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:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPAIN	NM_001033002.4	MANE Select	c.630+365A>G	intron	N/A	NP_001028174.2
RPAIN	NR_027679.2		n.912A>G	non_coding_transcript_exon	Exon 5 of 5
RPAIN	NM_001160243.2		c.*299A>G	3_prime_UTR	Exon 6 of 6	NP_001153715.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPAIN	ENST00000381209.8	TSL:1 MANE Select	c.630+365A>G	intron	N/A	ENSP00000370606.3
RPAIN	ENST00000381208.9	TSL:1	c.489+2277A>G	intron	N/A	ENSP00000370605.5
RPAIN	ENST00000536255.6	TSL:1	c.314-3966A>G	intron	N/A	ENSP00000439939.2

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41478

AN:

151978

Hom.:

6941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.271

AC:

260131

AN:

961470

Hom.:

39916

Cov.:

AF XY:

0.276

AC XY:

127958

AN XY:

463306

show subpopulations

African (AFR)

AF:

0.168

AC:

3566

AN:

21234

American (AMR)

AF:

0.357

AC:

4164

AN:

11676

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

3164

AN:

11758

East Asian (EAS)

AF:

0.810

AC:

14055

AN:

17346

South Asian (SAS)

AF:

0.505

AC:

24962

AN:

49478

European-Finnish (FIN)

AF:

0.336

AC:

4031

AN:

11992

Middle Eastern (MID)

AF:

0.286

AC:

693

AN:

2426

European-Non Finnish (NFE)

AF:

0.243

AC:

194400

AN:

798484

Other (OTH)

AF:

0.299

AC:

11096

AN:

37076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

8435

16869

25304

33738

42173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7834

15668

23502

31336

39170

<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:

0.273

AC:

41503

AN:

152096

Hom.:

6943

Cov.:

AF XY:

0.285

AC XY:

21191

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.177

AC:

7330

AN:

41492

American (AMR)

AF:

0.318

AC:

4858

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

887

AN:

3462

East Asian (EAS)

AF:

0.817

AC:

4216

AN:

5162

South Asian (SAS)

AF:

0.529

AC:

2554

AN:

4826

European-Finnish (FIN)

AF:

0.369

AC:

3892

AN:

10550

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.250

AC:

16967

AN:

67996

Other (OTH)

AF:

0.268

AC:

565

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1448

2896

4345

5793

7241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.256

Hom.:

868

Bravo

AF:

0.264

Asia WGS

AF:

0.612

AC:

2122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over