Genetic Variant ENST00000441148.1:n.236T>G (chr10-13058441-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 ENST00000441148.1(RPL5P25):n.236T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 760,780 control chromosomes in the GnomAD database, including 42,061 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 0.35 ( 9652 hom., cov: 33)

Exomes 𝑓: 0.32 ( 32409 hom. )

Consequence

RPL5P25
ENST00000441148.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.777

Publications

2 publications found

Variant links:

Genes affected

RPL5P25 (HGNC:35493): (ribosomal protein L5 pseudogene 25)

RPL5P25 links:

CCDC3 (HGNC:23813): (coiled-coil domain containing 3) Involved in negative regulation of gene expression; negative regulation of lipid metabolic process; and negative regulation of tumor necrosis factor-mediated signaling pathway. Located in endoplasmic reticulum and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CCDC3 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=-0.62).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL5P25		n.13058441A>C		intragenic_variant
CCDC3	NM_001282658.2 link	c.-269-8500T>G		intron_variant	Intron 4 of 6		NP_001269587.1	Q9BQI4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL5P25	ENST00000441148.1 link	n.236T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
CCDC3	ENST00000378839.1 link	c.-269-8500T>G		intron_variant	Intron 4 of 6	2		ENSP00000368116.1		Q9BQI4-2

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53272

AN:

152016

Hom.:

9646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.316

AC:

192362

AN:

608646

Hom.:

32409

Cov.:

AF XY:

0.309

AC XY:

102716

AN XY:

332106

show subpopulations

African (AFR)

AF:

0.407

AC:

7139

AN:

17542

American (AMR)

AF:

0.349

AC:

15128

AN:

43326

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

6960

AN:

20654

East Asian (EAS)

AF:

0.143

AC:

5142

AN:

35848

South Asian (SAS)

AF:

0.191

AC:

13269

AN:

69558

European-Finnish (FIN)

AF:

0.284

AC:

10582

AN:

37324

Middle Eastern (MID)

AF:

0.305

AC:

753

AN:

2466

European-Non Finnish (NFE)

AF:

0.351

AC:

122851

AN:

349634

Other (OTH)

AF:

0.326

AC:

10538

AN:

32294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

6099

12198

18296

24395

30494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.350

AC:

53310

AN:

152134

Hom.:

9652

Cov.:

AF XY:

0.346

AC XY:

25721

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.400

AC:

16582

AN:

41504

American (AMR)

AF:

0.374

AC:

5720

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1167

AN:

3466

East Asian (EAS)

AF:

0.132

AC:

683

AN:

5176

South Asian (SAS)

AF:

0.190

AC:

915

AN:

4822

European-Finnish (FIN)

AF:

0.279

AC:

2955

AN:

10592

Middle Eastern (MID)

AF:

0.332

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.354

AC:

24037

AN:

67988

Other (OTH)

AF:

0.329

AC:

694

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1805

3610

5415

7220

9025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.348

Hom.:

1182

Bravo

AF:

0.364

Asia WGS

AF:

0.168

AC:

584

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.4

(source)

DANN

Benign

0.37

PhyloP100

0.78

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

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