1-23692463-T-C

Position:

• chr1-23692463-T-C

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.7-146T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 975,720 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (177 hom., cov: 32)
  • Exomes 𝑓: 0.015 (177 hom.)
• Consequence: RPL11 NM_000975.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0720

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-23692463-T-C is Benign according to our data. Variant chr1-23692463-T-C is described in ClinVar as [Benign]. Clinvar id is 1251916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL11	NM_000975.5	c.7-146T>C		intron_variant		ENST00000643754.2	NP_000966.2
RPL11	NM_001199802.1	c.7-149T>C		intron_variant			NP_001186731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL11	ENST00000643754.2	c.7-146T>C		intron_variant			NM_000975.5	ENSP00000496250	A1

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5217 AN: 152128 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00914

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0350

GnomAD4 exome AF: 0.0146 AC: 11992 AN: 823474 Hom.: 177 Cov.: 11 AF XY: 0.0141 AC XY: 5977 AN XY: 424394

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.0166

Gnomad4 ASJ exome AF: 0.00774

Gnomad4 EAS exome AF: 0.0373

Gnomad4 SAS exome AF: 0.00886

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.0230

GnomAD4 genome AF: 0.0344 AC: 5234 AN: 152246 Hom.: 177 Cov.: 32 AF XY: 0.0329 AC XY: 2447 AN XY: 74450

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.00914

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0361

Alfa AF: 0.0255 Hom.: 10

Bravo AF: 0.0367

Asia WGS AF: 0.0410 AC: 142 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	-0.83
CADD	Benign	6.8
DANN	Benign	0.42

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: rs78796509; hg19: chr1-24018953;