2-101002821-C-G

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: 0.335

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL31	NM_000993.5	c.107+13C>G		intron_variant		ENST00000264258.8
RPL31	NM_001098577.3	c.107+13C>G		intron_variant
RPL31	NM_001099693.2	c.107+13C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL31	ENST00000264258.8	c.107+13C>G		intron_variant		1	NM_000993.5	P1

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

GnomAD3 exomes AF: 0.800 AC: 200119 AN: 250094 Hom.: 80399 AF XY: 0.797 AC XY: 107855 AN XY: 135246

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 SAS exome AF: 0.753

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

Gnomad4 AFR exome AF: 0.952

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.829

Gnomad4 EAS exome AF: 0.718

Gnomad4 SAS exome AF: 0.749

Gnomad4 FIN exome AF: 0.758

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.807

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

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.835

Alfa AF: 0.803 Hom.: 5807

Bravo AF: 0.853

Asia WGS AF: 0.738 AC: 2569 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	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.7
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2278724; hg19: chr2-101619283; COSMIC: COSV51821244; COSMIC: COSV51821244;