17-42998454-G-C

Variant names:

• chr17-42998454-G-C
• rs9899458
• NM_000988.5:c.-20G>C

Variant summary

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

The NM_000988.5(RPL27):​c.-20G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 299,454 control chromosomes in the GnomAD database, including 146,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73381 hom., cov: 31)
  • Exomes 𝑓: 1.0 (73350 hom.)
• Consequence: RPL27 NM_000988.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.939
• Publications: 4 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=-0.99).
• BP6: Variant 17-42998454-G-C is Benign according to our data. Variant chr17-42998454-G-C is described in ClinVar as Benign. ClinVar VariationId is 1240832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000988.5. 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.-20G>C		5_prime_UTR	Exon 1 of 5	NP_000979.1	P61353
	RPL27	NM_001349922.2		c.-297G>C		5_prime_UTR	Exon 1 of 4	NP_001336851.1	P61353
	RPL27	NM_001349921.2		c.-3+39G>C		intron	N/A	NP_001336850.1	P61353

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	ENST00000253788.12	TSL:1 MANE Select	c.-20G>C		5_prime_UTR	Exon 1 of 5	ENSP00000253788.5	P61353
	RPL27	ENST00000911442.1		c.-20G>C		5_prime_UTR	Exon 1 of 6	ENSP00000581501.1
	RPL27	ENST00000905376.1		c.-81G>C		5_prime_UTR	Exon 1 of 5	ENSP00000575435.1

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149298 AN: 152110 Hom.: 73332 Cov.: 31

Gnomad AFR AF: 0.936

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.984

GnomAD4 exome AF: 0.998 AC: 146958 AN: 147226 Hom.: 73350 Cov.: 0 AF XY: 0.998 AC XY: 79802 AN XY: 79946

African (AFR) AF: 0.942 AC: 2750 AN: 2920

American (AMR) AF: 0.995 AC: 4005 AN: 4026

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4124 AN: 4124

East Asian (EAS) AF: 1.00 AC: 5941 AN: 5942

South Asian (SAS) AF: 1.00 AC: 24855 AN: 24862

European-Finnish (FIN) AF: 1.00 AC: 8162 AN: 8162

Middle Eastern (MID) AF: 0.995 AC: 581 AN: 584

European-Non Finnish (NFE) AF: 1.00 AC: 88470 AN: 88500

Other (OTH) AF: 0.996 AC: 8070 AN: 8106

GnomAD4 genome AF: 0.981 AC: 149406 AN: 152228 Hom.: 73381 Cov.: 31 AF XY: 0.982 AC XY: 73064 AN XY: 74414

African (AFR) AF: 0.936 AC: 38833 AN: 41506

American (AMR) AF: 0.994 AC: 15193 AN: 15288

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

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4820 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10602 AN: 10602

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68019 AN: 68038

Other (OTH) AF: 0.984 AC: 2080 AN: 2114

Alfa AF: 0.988 Hom.: 9039

Bravo AF: 0.979

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	-0.99
CADD	Benign	3.6
DANN	Benign	0.72
PhyloP100		-0.94
PromoterAI		0.20	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs9899458; hg19: chr17-41150471;