Genetic Variant RPA3:c.99+66C>T (chr7-7640254-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000223129.8(RPA3):c.99+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,519,680 control chromosomes in the GnomAD database, including 7,685 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 0.081 ( 698 hom., cov: 32)

Exomes 𝑓: 0.096 ( 6987 hom. )

Consequence

RPA3
ENST00000223129.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0630

Publications

19 publications found

Variant links:

Genes affected

RPA3 (HGNC:10291): (replication protein A3) Enables damaged DNA binding activity and single-stranded DNA binding activity. Involved in DNA repair and DNA replication. Part of DNA replication factor A complex. [provided by Alliance of Genome Resources, Apr 2022]

RPA3 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=-0.75).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000223129.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPA3	NM_002947.5	MANE Select	c.99+66C>T		intron	N/A	NP_002938.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPA3	ENST00000223129.8	TSL:1 MANE Select	c.99+66C>T	intron	N/A	ENSP00000223129.4
RPA3	ENST00000396682.6	TSL:3	c.99+66C>T	intron	N/A	ENSP00000379914.2
RPA3	ENST00000406109.5	TSL:3	c.-19+469C>T	intron	N/A	ENSP00000384652.1

Frequencies

GnomAD3 genomes

AF:

0.0812

AC:

12352

AN:

152072

Hom.:

692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0208

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.0929

Gnomad SAS

AF:

0.0999

Gnomad FIN

AF:

0.0971

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0931

Gnomad OTH

AF:

0.0891

GnomAD4 exome

AF:

0.0957

AC:

130901

AN:

1367490

Hom.:

6987

Cov.:

AF XY:

0.0951

AC XY:

65174

AN XY:

685362

show subpopulations

African (AFR)

AF:

0.0164

AC:

515

AN:

31450

American (AMR)

AF:

0.221

AC:

9808

AN:

44304

Ashkenazi Jewish (ASJ)

AF:

0.0859

AC:

2195

AN:

25562

East Asian (EAS)

AF:

0.102

AC:

4016

AN:

39184

South Asian (SAS)

AF:

0.0993

AC:

8369

AN:

84320

European-Finnish (FIN)

AF:

0.0871

AC:

4575

AN:

52546

Middle Eastern (MID)

AF:

0.0967

AC:

537

AN:

5552

European-Non Finnish (NFE)

AF:

0.0929

AC:

95465

AN:

1027374

Other (OTH)

AF:

0.0948

AC:

5421

AN:

57198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5825

11650

17474

23299

29124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3458

6916

10374

13832

17290

<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:

0.0813

AC:

12373

AN:

152190

Hom.:

698

Cov.:

AF XY:

0.0831

AC XY:

6183

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0209

AC:

868

AN:

41544

American (AMR)

AF:

0.162

AC:

2481

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0847

AC:

294

AN:

3470

East Asian (EAS)

AF:

0.0929

AC:

481

AN:

5176

South Asian (SAS)

AF:

0.100

AC:

484

AN:

4830

European-Finnish (FIN)

AF:

0.0971

AC:

1026

AN:

10570

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0931

AC:

6328

AN:

67992

Other (OTH)

AF:

0.0891

AC:

188

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

563

1126

1690

2253

2816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0911

Hom.:

1210

Bravo

AF:

0.0860

Asia WGS

AF:

0.117

AC:

406

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.9

(source)

DANN

Benign

0.85

PhyloP100

-0.063

PromoterAI

0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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