Variant chr19-55391634-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000991.5(RPL28):c.*3302T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,546,214 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 60 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 39 hom. )

Consequence

RPL28
NM_000991.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.903

Variant links:

Genes affected

RPL28 (HGNC:10330): (ribosomal protein L28) 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 L28E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

RPL28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-55391634-T-C is Benign according to our data. Variant chr19-55391634-T-C is described in ClinVar as [Benign]. Clinvar id is 775430.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (2278/152350) while in subpopulation AFR AF= 0.0514 (2136/41582). AF 95% confidence interval is 0.0496. There are 60 homozygotes in gnomad4. There are 1117 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2278 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPL28	NM_000991.5 linkuse as main transcript	c.*3302T>C		3_prime_UTR_variant	5/5	ENST00000344063.7
RPL28	NM_001136135.2 linkuse as main transcript	c.405T>C	p.Cys135=	synonymous_variant	5/5
RPL28	NM_001136134.1 linkuse as main transcript	c.*3418T>C		3_prime_UTR_variant	4/4
RPL28	NM_001363697.1 linkuse as main transcript	c.324+3586T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL28	ENST00000344063.7 linkuse as main transcript	c.*3302T>C		3_prime_UTR_variant	5/5	1	NM_000991.5	P1	P46779-1
RPL28	ENST00000426763.3 linkuse as main transcript	n.5154T>C		non_coding_transcript_exon_variant	2/2	1
RPL28	ENST00000558815.5 linkuse as main transcript	c.405T>C	p.Cys135=	synonymous_variant	5/5	2			P46779-3
RPL28	ENST00000560055.5 linkuse as main transcript	c.324+3586T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2269

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00370

AC:

561

AN:

151642

Hom.:

AF XY:

0.00278

AC XY:

224

AN XY:

80642

show subpopulations

Gnomad AFR exome

AF:

0.0552

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000297

Gnomad OTH exome

AF:

0.00301

GnomAD4 exome

AF:

0.00159

AC:

2211

AN:

1393864

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

972

AN XY:

687660

show subpopulations

Gnomad4 AFR exome

AF:

0.0504

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.0150

AC:

2278

AN:

152350

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1117

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00654

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

DANN

Benign

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over