Genetic Variant RPL4:c.4-113T>C (chr15-66503642-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_000968.4(RPL4):c.4-113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,171,732 control chromosomes in the GnomAD database, including 434,812 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 0.89 ( 60642 hom., cov: 33)

Exomes 𝑓: 0.86 ( 374170 hom. )

Consequence

RPL4
NM_000968.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.213

Publications

7 publications found

Variant links:

Genes affected

RPL4 (HGNC:10353): (ribosomal protein L4) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L4E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL4 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000968.4. 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
	RPL4	NM_000968.4	MANE Select	c.4-113T>C		intron	N/A	NP_000959.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPL4	ENST00000307961.11	TSL:1 MANE Select	c.4-113T>C	intron	N/A	ENSP00000311430.6
RPL4	ENST00000568588.5	TSL:2	c.-279-113T>C	intron	N/A	ENSP00000454281.1
RPL4	ENST00000569696.5	TSL:5	c.4-113T>C	intron	N/A	ENSP00000457442.1

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135540

AN:

152156

Hom.:

60597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.866

Gnomad AMR

AF:

0.875

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.931

Gnomad SAS

AF:

0.922

Gnomad FIN

AF:

0.851

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.848

Gnomad OTH

AF:

0.884

GnomAD4 exome

AF:

0.856

AC:

872710

AN:

1019458

Hom.:

374170

AF XY:

0.857

AC XY:

428506

AN XY:

499742

show subpopulations

African (AFR)

AF:

0.977

AC:

22426

AN:

22946

American (AMR)

AF:

0.864

AC:

14843

AN:

17172

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

14671

AN:

16762

East Asian (EAS)

AF:

0.912

AC:

29856

AN:

32736

South Asian (SAS)

AF:

0.924

AC:

46660

AN:

50498

European-Finnish (FIN)

AF:

0.843

AC:

37080

AN:

43964

Middle Eastern (MID)

AF:

0.920

AC:

4268

AN:

4640

European-Non Finnish (NFE)

AF:

0.845

AC:

664566

AN:

786854

Other (OTH)

AF:

0.874

AC:

38340

AN:

43886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6110

12219

18329

24438

30548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14750

29500

44250

59000

73750

<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:

0.891

AC:

135641

AN:

152274

Hom.:

60642

Cov.:

AF XY:

0.893

AC XY:

66452

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.971

AC:

40359

AN:

41562

American (AMR)

AF:

0.875

AC:

13378

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

3030

AN:

3470

East Asian (EAS)

AF:

0.930

AC:

4827

AN:

5188

South Asian (SAS)

AF:

0.922

AC:

4446

AN:

4820

European-Finnish (FIN)

AF:

0.851

AC:

9023

AN:

10598

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.848

AC:

57646

AN:

68018

Other (OTH)

AF:

0.885

AC:

1873

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

761

1521

2282

3042

3803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.857

Hom.:

17488

Bravo

AF:

0.894

Asia WGS

AF:

0.927

AC:

3223

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.8

(source)

DANN

Benign

0.37

PhyloP100

0.21

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