Genetic Variant NM_001033002.4:c.252+107A>C (chr17-5421573-A-C) – 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.252+107A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 948,114 control chromosomes in the GnomAD database, including 53,583 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 ( 7977 hom., cov: 31)

Exomes 𝑓: 0.31 ( 45606 hom. )

Consequence

RPAIN
NM_001033002.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.304

Publications

9 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:

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=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPAIN	NM_001033002.4 link	c.252+107A>C		intron_variant	Intron 2 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.252+107A>C		intron_variant	Intron 2 of 6	1	NM_001033002.4	ENSP00000370606.3		Q86UA6-1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45204

AN:

151492

Hom.:

7966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.310

AC:

247132

AN:

796504

Hom.:

45606

Cov.:

AF XY:

0.317

AC XY:

128211

AN XY:

403828

show subpopulations

African (AFR)

AF:

0.187

AC:

3429

AN:

18338

American (AMR)

AF:

0.399

AC:

7607

AN:

19050

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

4874

AN:

15772

East Asian (EAS)

AF:

0.800

AC:

25649

AN:

32052

South Asian (SAS)

AF:

0.526

AC:

26718

AN:

50762

European-Finnish (FIN)

AF:

0.391

AC:

16473

AN:

42180

Middle Eastern (MID)

AF:

0.356

AC:

933

AN:

2624

European-Non Finnish (NFE)

AF:

0.258

AC:

149503

AN:

578864

Other (OTH)

AF:

0.324

AC:

11946

AN:

36862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7599

15198

22796

30395

37994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4072

8144

12216

16288

20360

<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:

0.298

AC:

45250

AN:

151610

Hom.:

7977

Cov.:

AF XY:

0.312

AC XY:

23090

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.200

AC:

8265

AN:

41306

American (AMR)

AF:

0.349

AC:

5314

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1075

AN:

3462

East Asian (EAS)

AF:

0.816

AC:

4207

AN:

5156

South Asian (SAS)

AF:

0.542

AC:

2595

AN:

4792

European-Finnish (FIN)

AF:

0.410

AC:

4303

AN:

10486

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18571

AN:

67856

Other (OTH)

AF:

0.313

AC:

659

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1472

2944

4416

5888

7360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.289

Hom.:

3569

Bravo

AF:

0.288

Asia WGS

AF:

0.623

AC:

2161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.2

(source)

DANN

Benign

0.44

PhyloP100

-0.30

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