17-42998504-C-T

Position:

• chr17-42998504-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000589913.6(RPL27):​c.-247C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 402,574 control chromosomes in the GnomAD database, including 191,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (67476 hom., cov: 31)
  • Exomes 𝑓: 0.99 (123725 hom.)
• Consequence: RPL27 ENST00000589913.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.312

Genes affected

RPL27 (HGNC:10328): (ribosomal protein L27) 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 L27e family of ribosomal proteins and a component of the 60S subunit. A splice site mutation in this gene has been identified in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

LOC124904006 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-42998504-C-T is Benign according to our data. Variant chr17-42998504-C-T is described in ClinVar as [Benign]. Clinvar id is 1182827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL27	NM_000988.5	c.-3+33C>T		intron_variant		ENST00000253788.12	NP_000979.1
LOC124904006	XR_007065759.1	n.1096G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL27	ENST00000253788.12	c.-3+33C>T		intron_variant		1	NM_000988.5	ENSP00000253788	P1

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142430 AN: 152034 Hom.: 67436 Cov.: 31

Gnomad AFR AF: 0.779

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.956

GnomAD4 exome AF: 0.994 AC: 248819 AN: 250422 Hom.: 123725 Cov.: 2 AF XY: 0.995 AC XY: 133215 AN XY: 133916

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.984

GnomAD4 genome AF: 0.937 AC: 142525 AN: 152152 Hom.: 67476 Cov.: 31 AF XY: 0.938 AC XY: 69796 AN XY: 74378

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.956

Alfa AF: 0.947 Hom.: 3970

Bravo AF: 0.928

Asia WGS AF: 0.982 AC: 3413 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	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs691997; hg19: chr17-41150521;