1-23691897-G-T

Variant names:

• chr1-23691897-G-T
• rs72870597
• NM_000975.5:c.6+68G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000975.5. 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
	RPL11	NM_000975.5	MANE Select	c.6+68G>T		intron	N/A	NP_000966.2
	RPL11	NM_001199802.1		c.6+68G>T		intron	N/A	NP_001186731.1	P62913-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL11	ENST00000643754.2	MANE Select	c.6+68G>T		intron	N/A	ENSP00000496250.1	P62913-1
	RPL11	ENST00000374550.8	TSL:1	c.6+68G>T		intron	N/A	ENSP00000363676.4	P62913-2
	RPL11	ENST00000933799.1		c.6+68G>T		intron	N/A	ENSP00000603858.1

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

African (AFR) AF: 0.0800 AC: 2664 AN: 33308

American (AMR) AF: 0.00702 AC: 314 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 270 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.000476 AC: 41 AN: 86082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.0136 AC: 78 AN: 5730

European-Non Finnish (NFE) AF: 0.000545 AC: 602 AN: 1104002

Other (OTH) AF: 0.00749 AC: 450 AN: 60088

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

African (AFR) AF: 0.0787 AC: 3273 AN: 41574

American (AMR) AF: 0.0112 AC: 172 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68030

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0191 Hom.: 6

Bravo AF: 0.0266

Asia WGS AF: 0.00664 AC: 24 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
AlphaMissense	Benign	0.23
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.71
PhyloP100		0.13
PromoterAI		-0.0052	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism

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: rs72870597; hg19: chr1-24018387;