2-101002821-C-G

Variant names:

• chr2-101002821-C-G
• rs2278724
• NM_000993.5:c.107+13C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000993.5(RPL31):​c.107+13C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,600,106 control chromosomes in the GnomAD database, including 528,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54566 hom., cov: 32)
  • Exomes 𝑓: 0.81 (474389 hom.)
• Consequence: RPL31 NM_000993.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.335
• Publications: 9 publications found

Genes affected

RPL31 (HGNC:10334): (ribosomal protein L31) 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 L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RPL31 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-101002821-C-G is Benign according to our data. Variant chr2-101002821-C-G is described in ClinVar as Benign. ClinVar VariationId is 1269137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000993.5. 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
	RPL31	NM_000993.5	MANE Select	c.107+13C>G		intron	N/A	NP_000984.1	P62899-1
	RPL31	NM_001098577.3		c.107+13C>G		intron	N/A	NP_001092047.1	P62899-2
	RPL31	NM_001099693.2		c.107+13C>G		intron	N/A	NP_001093163.1	P62899-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL31	ENST00000264258.8	TSL:1 MANE Select	c.107+13C>G		intron	N/A	ENSP00000264258.3	P62899-1
	RPL31	ENST00000409733.5	TSL:1	c.107+13C>G		intron	N/A	ENSP00000386681.1	P62899-1
	RPL31	ENST00000409320.7	TSL:1	c.107+13C>G		intron	N/A	ENSP00000387163.3	P62899-3

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128257 AN: 151992 Hom.: 54513 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.841

GnomAD2 exomes AF: 0.800 AC: 200119 AN: 250094 AF XY: 0.797

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.824

Gnomad EAS exome AF: 0.740

Gnomad FIN exome AF: 0.757

Gnomad NFE exome AF: 0.816

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.808 AC: 1170557 AN: 1447996 Hom.: 474389 Cov.: 27 AF XY: 0.807 AC XY: 581777 AN XY: 721230

African (AFR) AF: 0.952 AC: 31641 AN: 33226

American (AMR) AF: 0.778 AC: 34757 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 21561 AN: 26018

East Asian (EAS) AF: 0.718 AC: 28423 AN: 39600

South Asian (SAS) AF: 0.749 AC: 64368 AN: 85930

European-Finnish (FIN) AF: 0.758 AC: 40480 AN: 53394

Middle Eastern (MID) AF: 0.833 AC: 4782 AN: 5740

European-Non Finnish (NFE) AF: 0.815 AC: 896203 AN: 1099534

Other (OTH) AF: 0.807 AC: 48342 AN: 59900

GnomAD4 genome AF: 0.844 AC: 128365 AN: 152110 Hom.: 54566 Cov.: 32 AF XY: 0.839 AC XY: 62357 AN XY: 74310

African (AFR) AF: 0.948 AC: 39380 AN: 41540

American (AMR) AF: 0.818 AC: 12504 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2854 AN: 3472

East Asian (EAS) AF: 0.718 AC: 3700 AN: 5156

South Asian (SAS) AF: 0.758 AC: 3646 AN: 4810

European-Finnish (FIN) AF: 0.755 AC: 7972 AN: 10558

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55644 AN: 67974

Other (OTH) AF: 0.835 AC: 1763 AN: 2112

Alfa AF: 0.803 Hom.: 5807

Bravo AF: 0.853

Asia WGS AF: 0.738 AC: 2569 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.43
PhyloP100		0.34
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2278724; hg19: chr2-101619283; COSMIC: COSV51821244; COSMIC: COSV51821244;