Genetic Variant RSRP1:p.Glu239Gly (chr1-25243590-T-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_020317.5(RSRP1):c.716A>G(p.Glu239Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,613,258 control chromosomes in the GnomAD database, including 47,036 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3451 hom., cov: 32)

Exomes 𝑓: 0.23 ( 43585 hom. )

Consequence

RSRP1
NM_020317.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

56 publications found

Variant links:

Genes affected

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

RSRP1 links:

ENSG00000284657 (HGNC:):

ENSG00000284657 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 (MetaRNN=0.004683733).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRP1	NM_020317.5 link	c.716A>G	p.Glu239Gly	missense_variant	Exon 4 of 5	ENST00000243189.12	NP_064713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRP1	ENST00000243189.12 link	c.716A>G	p.Glu239Gly	missense_variant	Exon 4 of 5	1	NM_020317.5	ENSP00000243189.7

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28438

AN:

152110

Hom.:

3450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.222

GnomAD2 exomes

AF:

0.202

AC:

50877

AN:

251340

AF XY:

0.208

show subpopulations

Gnomad AFR exome

AF:

0.0445

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.384

Gnomad EAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.234

AC:

341409

AN:

1461030

Hom.:

43585

Cov.:

AF XY:

0.233

AC XY:

169387

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.0432

AC:

1447

AN:

33462

American (AMR)

AF:

0.154

AC:

6864

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

9972

AN:

26108

East Asian (EAS)

AF:

0.0160

AC:

635

AN:

39618

South Asian (SAS)

AF:

0.115

AC:

9893

AN:

86210

European-Finnish (FIN)

AF:

0.259

AC:

13821

AN:

53364

Middle Eastern (MID)

AF:

0.347

AC:

1997

AN:

5756

European-Non Finnish (NFE)

AF:

0.254

AC:

282668

AN:

1111466

Other (OTH)

AF:

0.234

AC:

14112

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12403

24806

37208

49611

62014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9174

18348

27522

36696

45870

<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:

0.187

AC:

28437

AN:

152228

Hom.:

3451

Cov.:

AF XY:

0.186

AC XY:

13843

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0504

AC:

2093

AN:

41564

American (AMR)

AF:

0.199

AC:

3039

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1331

AN:

3472

East Asian (EAS)

AF:

0.0233

AC:

121

AN:

5190

South Asian (SAS)

AF:

0.108

AC:

524

AN:

4832

European-Finnish (FIN)

AF:

0.263

AC:

2784

AN:

10588

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17724

AN:

67980

Other (OTH)

AF:

0.221

AC:

467

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1115

2230

3345

4460

5575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.234

Hom.:

19561

Bravo

AF:

0.177

TwinsUK

AF:

0.261

AC:

968

ALSPAC

AF:

0.259

AC:

998

ESP6500AA

AF:

0.0538

AC:

237

ESP6500EA

AF:

0.268

AC:

2306

ExAC

AF:

0.200

AC:

24236

Asia WGS

AF:

0.0900

AC:

313

AN:

3476

EpiCase

AF:

0.276

EpiControl

AF:

0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

2.0

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.088

Sift

Uncertain

0.0070

Sift4G

Benign

0.30

Vest4

0.086

ClinPred

0.031

GERP RS

4.0

Varity_R

0.19

gMVP

0.30

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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