17-42998932-G-A

Position:

• chr17-42998932-G-A

Variant summary

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

The NM_000988.5(RPL27):​c.81+101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 895,796 control chromosomes in the GnomAD database, including 183,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (24656 hom., cov: 32)
  • Exomes 𝑓: 0.65 (158918 hom.)
• Consequence: RPL27 NM_000988.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34

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=-0.91).
• BP6: Variant 17-42998932-G-A is Benign according to our data. Variant chr17-42998932-G-A is described in ClinVar as [Benign]. Clinvar id is 1251530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL27	NM_000988.5	c.81+101G>A		intron_variant		ENST00000253788.12	NP_000979.1
LOC124904006	XR_007065759.1	n.668C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL27	ENST00000253788.12	c.81+101G>A		intron_variant		1	NM_000988.5	ENSP00000253788	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80786 AN: 151910 Hom.: 24647 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.567

GnomAD3 exomes AF: 0.631 AC: 127623 AN: 202346 Hom.: 41737 AF XY: 0.633 AC XY: 69755 AN XY: 110186

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.764

Gnomad ASJ exome AF: 0.636

Gnomad EAS exome AF: 0.553

Gnomad SAS exome AF: 0.560

Gnomad FIN exome AF: 0.598

Gnomad NFE exome AF: 0.685

Gnomad OTH exome AF: 0.651

GnomAD4 exome AF: 0.647 AC: 480992 AN: 743768 Hom.: 158918 Cov.: 10 AF XY: 0.645 AC XY: 253628 AN XY: 393216

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.748

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.569

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.621

GnomAD4 genome AF: 0.531 AC: 80798 AN: 152028 Hom.: 24656 Cov.: 32 AF XY: 0.532 AC XY: 39500 AN XY: 74306

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.563

Alfa AF: 0.642 Hom.: 18895

Bravo AF: 0.525

Asia WGS AF: 0.501 AC: 1741 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	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2271539; hg19: chr17-41150949; COSMIC: COSV53815560;