19-55391634-T-C

Position:

• chr19-55391634-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.903

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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
RPL28	NM_000991.5	c.*3302T>C		3_prime_UTR_variant	5/5	ENST00000344063.7	NP_000982.2
RPL28	NM_001136135.2	c.405T>C	p.Cys135=	synonymous_variant	5/5		NP_001129607.1
RPL28	NM_001136134.1	c.*3418T>C		3_prime_UTR_variant	4/4		NP_001129606.1
RPL28	NM_001363697.1	c.324+3586T>C		intron_variant			NP_001350626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL28	ENST00000344063.7	c.*3302T>C		3_prime_UTR_variant	5/5	1	NM_000991.5	ENSP00000342787	P1
RPL28	ENST00000426763.3	n.5154T>C		non_coding_transcript_exon_variant	2/2	1
RPL28	ENST00000558815.5	c.405T>C	p.Cys135=	synonymous_variant	5/5	2		ENSP00000452909
RPL28	ENST00000560055.5	c.324+3586T>C		intron_variant		3		ENSP00000452763

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2269 AN: 152232 Hom.: 58 Cov.: 33

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.: 6 AF XY: 0.00278 AC XY: 224 AN XY: 80642

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.: 39 Cov.: 27 AF XY: 0.00141 AC XY: 972 AN XY: 687660

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.: 60 Cov.: 33 AF XY: 0.0150 AC XY: 1117 AN XY: 74500

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.: 19

Bravo AF: 0.0168

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

Other links and lift over

dbSNP: rs7260639; hg19: chr19-55903002;