2-101002859-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000993.5(RPL31):c.107+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,363,574 control chromosomes in the GnomAD database, including 291,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29926 hom., cov: 31)
  • Exomes 𝑓: 0.65 (261281 hom.)
• Consequence: RPL31 NM_000993.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-101002859-T-C is Benign according to our data. Variant chr2-101002859-T-C is described in ClinVar as [Benign]. Clinvar id is 1246390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL31	NM_000993.5	c.107+51T>C		intron_variant		ENST00000264258.8
RPL31	NM_001098577.3	c.107+51T>C		intron_variant
RPL31	NM_001099693.2	c.107+51T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL31	ENST00000264258.8	c.107+51T>C		intron_variant		1	NM_000993.5	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94391 AN: 151804 Hom.: 29915 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.645

GnomAD3 exomes AF: 0.614 AC: 148973 AN: 242492 Hom.: 46892 AF XY: 0.619 AC XY: 81289 AN XY: 131344

Gnomad AFR exome AF: 0.556

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.331

Gnomad SAS exome AF: 0.586

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.683

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.653 AC: 790693 AN: 1211650 Hom.: 261281 Cov.: 17 AF XY: 0.652 AC XY: 400158 AN XY: 613798

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.749

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.622 AC: 94441 AN: 151924 Hom.: 29926 Cov.: 31 AF XY: 0.617 AC XY: 45765 AN XY: 74210

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.642

Alfa AF: 0.669 Hom.: 23155

Bravo AF: 0.619

Asia WGS AF: 0.462 AC: 1612 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.80
Cadd	Benign	6.9
Dann	Benign	0.74
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: rs2278723; hg19: chr2-101619321; COSMIC: COSV51821475; COSMIC: COSV51821475;