rs10874744

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000969.5(RPL5):c.794+121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 795,566 control chromosomes in the GnomAD database, including 176,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28658 hom., cov: 32)

Exomes 𝑓: 0.67 ( 147532 hom. )

Consequence

RPL5
NM_000969.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.109

Publications

18 publications found

Variant links:

Genes affected

RPL5 (HGNC:10360): (ribosomal protein L5) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Mar 2017]

RPL5 links:

DIPK1A (HGNC:32213): (divergent protein kinase domain 1A) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

DIPK1A links:

SNORA66 (HGNC:10223): (small nucleolar RNA, H/ACA box 66) This gene encodes a non-coding RNA that functions in the biogenesis of other small nuclear RNAs. This RNA is found in the nucleolus, where it may be involved in the pseudouridylation of 18S ribosomal RNA. This RNA is found associated with the GAR1 protein. [provided by RefSeq, Apr 2009]

SNORA66 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 1-92840760-G-A is Benign according to our data. Variant chr1-92840760-G-A is described in ClinVar as Benign. ClinVar VariationId is 298213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000969.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL5	NM_000969.5	MANE Select	c.794+121G>A	intron	N/A	NP_000960.2
DIPK1A	NM_001252273.2		c.474+6423C>T	intron	N/A	NP_001239202.1	Q5T7M9-2
SNORA66	NR_002444.2		n.42G>A	non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL5	ENST00000370321.8	TSL:1 MANE Select	c.794+121G>A	intron	N/A	ENSP00000359345.2	P46777
DIPK1A	ENST00000615519.4	TSL:1	c.474+6423C>T	intron	N/A	ENSP00000483279.1	Q5T7M9-2
RPL5	ENST00000880515.1		c.788+121G>A	intron	N/A	ENSP00000550574.1

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91573

AN:

151864

Hom.:

28651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.701

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.947

Gnomad SAS

AF:

0.801

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.580

GnomAD2 exomes

AF:

0.686

AC:

160765

AN:

234464

AF XY:

0.688

show subpopulations

Gnomad AFR exome

AF:

0.459

Gnomad AMR exome

AF:

0.753

Gnomad ASJ exome

AF:

0.725

Gnomad EAS exome

AF:

0.947

Gnomad FIN exome

AF:

0.631

Gnomad NFE exome

AF:

0.622

Gnomad OTH exome

AF:

0.660

GnomAD4 exome

AF:

0.669

AC:

430561

AN:

643584

Hom.:

147532

Cov.:

AF XY:

0.675

AC XY:

236348

AN XY:

349904

show subpopulations

African (AFR)

AF:

0.450

AC:

8149

AN:

18116

American (AMR)

AF:

0.745

AC:

32185

AN:

43180

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

15075

AN:

20692

East Asian (EAS)

AF:

0.958

AC:

33798

AN:

35270

South Asian (SAS)

AF:

0.797

AC:

55499

AN:

69632

European-Finnish (FIN)

AF:

0.629

AC:

23078

AN:

36666

Middle Eastern (MID)

AF:

0.669

AC:

2791

AN:

4174

European-Non Finnish (NFE)

AF:

0.623

AC:

238417

AN:

382414

Other (OTH)

AF:

0.645

AC:

21569

AN:

33440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

7314

14628

21942

29256

36570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2188

4376

6564

8752

10940

<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:

0.603

AC:

91616

AN:

151982

Hom.:

28658

Cov.:

AF XY:

0.608

AC XY:

45170

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.464

AC:

19222

AN:

41446

American (AMR)

AF:

0.647

AC:

9873

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

2585

AN:

3468

East Asian (EAS)

AF:

0.947

AC:

4900

AN:

5176

South Asian (SAS)

AF:

0.801

AC:

3858

AN:

4814

European-Finnish (FIN)

AF:

0.614

AC:

6477

AN:

10556

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42653

AN:

67944

Other (OTH)

AF:

0.584

AC:

1234

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1801

3602

5403

7204

9005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.619

Hom.:

38043

Bravo

AF:

0.598

Asia WGS

AF:

0.801

AC:

2782

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Diamond-Blackfan anemia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

-0.11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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