17-42998504-C-T

Variant names:

• chr17-42998504-C-T
• rs691997
• ENST00000589913.6:c.-247C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349922.2(RPL27):​c.-247C>T variant causes a 5 prime UTR premature start codon gain 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 NM_001349922.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.312
• Publications: 3 publications found

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]

RPL27 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 16

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

LOC124904006 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	NM_000988.5	MANE Select	c.-3+33C>T		intron	N/A	NP_000979.1	P61353
	RPL27	NM_001349922.2		c.-247C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001336851.1	P61353
	RPL27	NM_001349922.2		c.-247C>T		5_prime_UTR	Exon 1 of 4	NP_001336851.1	P61353

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	ENST00000589913.6	TSL:1	c.-247C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000464813.1	P61353
	RPL27	ENST00000589913.6	TSL:1	c.-247C>T		5_prime_UTR	Exon 1 of 4	ENSP00000464813.1	P61353
	RPL27	ENST00000253788.12	TSL:1 MANE Select	c.-3+33C>T		intron	N/A	ENSP00000253788.5	P61353

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

African (AFR) AF: 0.796 AC: 4402 AN: 5530

American (AMR) AF: 0.982 AC: 6842 AN: 6964

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 7945 AN: 7946

East Asian (EAS) AF: 0.999 AC: 14252 AN: 14260

South Asian (SAS) AF: 0.999 AC: 31158 AN: 31174

European-Finnish (FIN) AF: 1.00 AC: 16073 AN: 16074

Middle Eastern (MID) AF: 0.994 AC: 1121 AN: 1128

European-Non Finnish (NFE) AF: 0.999 AC: 152787 AN: 152876

Other (OTH) AF: 0.984 AC: 14239 AN: 14470

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

African (AFR) AF: 0.779 AC: 32313 AN: 41466

American (AMR) AF: 0.980 AC: 14979 AN: 15284

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4809 AN: 4810

European-Finnish (FIN) AF: 1.00 AC: 10586 AN: 10586

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67976 AN: 68042

Other (OTH) AF: 0.956 AC: 2019 AN: 2112

Alfa AF: 0.935 Hom.: 4219

Bravo AF: 0.928

Asia WGS AF: 0.982 AC: 3413 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.92
PhyloP100		-0.31
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs691997; hg19: chr17-41150521;