rs691711

Variant names:

• chr17-42999726-G-A
• rs691711
• NM_000988.5:c.82-207G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-42999726-G-A
• chr17-42999726-G-T
• chr17-42999726-G-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.82-207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 549,774 control chromosomes in the GnomAD database, including 263,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (67537 hom., cov: 32)
  • Exomes 𝑓: 0.99 (195693 hom.)
• Consequence: RPL27 NM_000988.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630
• Publications: 1 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=-0.9).
• BP6: Variant 17-42999726-G-A is Benign according to our data. Variant chr17-42999726-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263870.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.82-207G>A		intron	N/A	NP_000979.1	P61353
	RPL27	NM_001349921.2		c.82-207G>A		intron	N/A	NP_001336850.1	P61353
	RPL27	NM_001349922.2		c.82-207G>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.82-207G>A		intron	N/A	ENSP00000253788.5	P61353
	RPL27	ENST00000589913.6	TSL:1	c.82-207G>A		intron	N/A	ENSP00000464813.1	P61353
	RPL27	ENST00000911442.1		c.172-207G>A		intron	N/A	ENSP00000581501.1

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142557 AN: 152156 Hom.: 67497 Cov.: 32

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: 0.957

GnomAD4 exome AF: 0.992 AC: 394170 AN: 397500 Hom.: 195693 Cov.: 3 AF XY: 0.993 AC XY: 206260 AN XY: 207688

African (AFR) AF: 0.786 AC: 9179 AN: 11676

American (AMR) AF: 0.983 AC: 15193 AN: 15454

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 12557 AN: 12558

East Asian (EAS) AF: 1.00 AC: 28884 AN: 28884

South Asian (SAS) AF: 0.999 AC: 36191 AN: 36212

European-Finnish (FIN) AF: 1.00 AC: 26628 AN: 26628

Middle Eastern (MID) AF: 0.993 AC: 1743 AN: 1756

European-Non Finnish (NFE) AF: 0.999 AC: 240824 AN: 240974

Other (OTH) AF: 0.983 AC: 22971 AN: 23358

GnomAD4 genome AF: 0.937 AC: 142651 AN: 152274 Hom.: 67537 Cov.: 32 AF XY: 0.938 AC XY: 69876 AN XY: 74456

African (AFR) AF: 0.779 AC: 32353 AN: 41514

American (AMR) AF: 0.980 AC: 14999 AN: 15300

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

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4823 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

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

European-Non Finnish (NFE) AF: 0.999 AC: 67973 AN: 68036

Other (OTH) AF: 0.957 AC: 2024 AN: 2114

Alfa AF: 0.946 Hom.: 11551

Bravo AF: 0.928

Asia WGS AF: 0.989 AC: 3437 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	-0.90
CADD	Benign	1.0
DANN	Benign	0.27
PhyloP100		-0.063
Mutation Taster		=100/0	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: rs691711; hg19: chr17-41151743;