17-42998932-G-A

Variant names:

• chr17-42998932-G-A
• rs2271539
• NM_000988.5:c.81+101G>A

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.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
• Publications: 19 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=-0.91).
• BP6: Variant 17-42998932-G-A is Benign according to our data. Variant chr17-42998932-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.81+101G>A		intron	N/A	NP_000979.1	P61353
	RPL27	NM_001349921.2		c.81+101G>A		intron	N/A	NP_001336850.1	P61353
	RPL27	NM_001349922.2		c.81+101G>A		intron	N/A	NP_001336851.1	P61353

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL27	ENST00000253788.12	TSL:1 MANE Select	c.81+101G>A		intron	N/A	ENSP00000253788.5	P61353
	RPL27	ENST00000589913.6	TSL:1	c.81+101G>A		intron	N/A	ENSP00000464813.1	P61353
	RPL27	ENST00000911441.1		c.182G>A	p.Ser61Asn	missense	Exon 2 of 4	ENSP00000581500.1

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

GnomAD2 exomes AF: 0.631 AC: 127623 AN: 202346 AF XY: 0.633

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 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

African (AFR) AF: 0.201 AC: 3985 AN: 19782

American (AMR) AF: 0.748 AC: 29222 AN: 39080

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 12262 AN: 19424

East Asian (EAS) AF: 0.569 AC: 20356 AN: 35772

South Asian (SAS) AF: 0.558 AC: 37559 AN: 67360

European-Finnish (FIN) AF: 0.598 AC: 25654 AN: 42922

Middle Eastern (MID) AF: 0.606 AC: 2604 AN: 4298

European-Non Finnish (NFE) AF: 0.682 AC: 326752 AN: 478758

Other (OTH) AF: 0.621 AC: 22598 AN: 36372

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

African (AFR) AF: 0.210 AC: 8725 AN: 41494

American (AMR) AF: 0.670 AC: 10234 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3466

East Asian (EAS) AF: 0.560 AC: 2884 AN: 5154

South Asian (SAS) AF: 0.559 AC: 2687 AN: 4810

European-Finnish (FIN) AF: 0.580 AC: 6121 AN: 10556

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45950 AN: 67968

Other (OTH) AF: 0.563 AC: 1187 AN: 2108

Alfa AF: 0.641 Hom.: 36603

Bravo AF: 0.525

Asia WGS AF: 0.501 AC: 1741 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	-0.91
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-1.3
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2271539; hg19: chr17-41150949; COSMIC: COSV53815560;