2-101002915-C-T

Position:

• chr2-101002915-C-T

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+107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 782,068 control chromosomes in the GnomAD database, including 6,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (977 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5236 hom.)
• Consequence: RPL31 NM_000993.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.107

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=-0.79).
• BP6: Variant 2-101002915-C-T is Benign according to our data. Variant chr2-101002915-C-T is described in ClinVar as [Benign]. Clinvar id is 1291849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL31	NM_000993.5	c.107+107C>T		intron_variant		ENST00000264258.8	NP_000984.1
RPL31	NM_001098577.3	c.107+107C>T		intron_variant			NP_001092047.1
RPL31	NM_001099693.2	c.107+107C>T		intron_variant			NP_001093163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL31	ENST00000264258.8	c.107+107C>T		intron_variant		1	NM_000993.5	ENSP00000264258	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15638 AN: 152002 Hom.: 977 Cov.: 32

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0685

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.119 AC: 75136 AN: 629946 Hom.: 5236 AF XY: 0.117 AC XY: 38995 AN XY: 332390

Gnomad4 AFR exome AF: 0.0503

Gnomad4 AMR exome AF: 0.0738

Gnomad4 ASJ exome AF: 0.0595

Gnomad4 EAS exome AF: 0.000539

Gnomad4 SAS exome AF: 0.0757

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.103 AC: 15641 AN: 152122 Hom.: 977 Cov.: 32 AF XY: 0.103 AC XY: 7642 AN XY: 74356

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.0965

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0531 Hom.: 54

Bravo AF: 0.0973

Asia WGS AF: 0.0300 AC: 107 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	May 17, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.6
DANN	Benign	0.71

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: rs72821045; hg19: chr2-101619377;