chr1-23691897-G-T

Position:

• chr1-23691897-G-T

Variant summary

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

The NM_000975.5(RPL11):​c.6+68G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,605,238 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (147 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (137 hom.)
• Consequence: RPL11 NM_000975.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.131

Genes affected

RPL11 (HGNC:10301): (ribosomal protein L11) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L5P family of ribosomal proteins. It is located in the cytoplasm. The protein probably associates with the 5S rRNA. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Dec 2010]

RPL11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-23691897-G-T is Benign according to our data. Variant chr1-23691897-G-T is described in ClinVar as [Benign]. Clinvar id is 1243261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL11	NM_000975.5	c.6+68G>T		intron_variant		ENST00000643754.2	NP_000966.2
RPL11	NM_001199802.1	c.6+68G>T		intron_variant			NP_001186731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL11	ENST00000643754.2	c.6+68G>T		intron_variant			NM_000975.5	ENSP00000496250.1
RPL11	ENST00000374550.8	c.6+68G>T		intron_variant		1		ENSP00000363676.4
RPL11	ENST00000467075.2	n.74G>T		non_coding_transcript_exon_variant	1/6	3		ENSP00000493634.1
RPL11	ENST00000443624.6	n.24+68G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3581 AN: 152224 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.00304 AC: 4419 AN: 1452896 Hom.: 137 Cov.: 29 AF XY: 0.00277 AC XY: 2006 AN XY: 723458

Gnomad4 AFR exome AF: 0.0800

Gnomad4 AMR exome AF: 0.00702

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000476

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000545

Gnomad4 OTH exome AF: 0.00749

GnomAD4 genome AF: 0.0236 AC: 3592 AN: 152342 Hom.: 147 Cov.: 32 AF XY: 0.0230 AC XY: 1716 AN XY: 74490

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0191 Hom.: 6

Bravo AF: 0.0266

Asia WGS AF: 0.00664 AC: 24 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	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.71
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs72870597; hg19: chr1-24018387;