2-101004304-C-G

Variant names:

• chr2-101004304-C-G
• rs13420285
• NM_000993.5:c.233+21C>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.233+21C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,611,914 control chromosomes in the GnomAD database, including 1,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (714 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (644 hom.)
• Consequence: RPL31 NM_000993.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37
• Publications: 4 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=-0.89).
• BP6: Variant 2-101004304-C-G is Benign according to our data. Variant chr2-101004304-C-G is described in ClinVar as Benign. ClinVar VariationId is 1233833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 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.233+21C>G		intron	N/A	NP_000984.1	P62899-1
	RPL31	NM_001098577.3		c.233+21C>G		intron	N/A	NP_001092047.1	P62899-2
	RPL31	NM_001099693.2		c.233+21C>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.233+21C>G		intron	N/A	ENSP00000264258.3	P62899-1
	RPL31	ENST00000409733.5	TSL:1	c.233+21C>G		intron	N/A	ENSP00000386681.1	P62899-1
	RPL31	ENST00000409320.7	TSL:1	c.233+21C>G		intron	N/A	ENSP00000387163.3	P62899-3

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7982 AN: 151692 Hom.: 711 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0352

GnomAD2 exomes AF: 0.0135 AC: 3345 AN: 247240 AF XY: 0.0100

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.00985

Gnomad ASJ exome AF: 0.00161

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000546

Gnomad OTH exome AF: 0.00780

GnomAD4 exome AF: 0.00563 AC: 8222 AN: 1460104 Hom.: 644 Cov.: 31 AF XY: 0.00488 AC XY: 3543 AN XY: 726270

African (AFR) AF: 0.190 AC: 6349 AN: 33402

American (AMR) AF: 0.0109 AC: 484 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000244 AC: 21 AN: 85936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53186

Middle Eastern (MID) AF: 0.0102 AC: 59 AN: 5766

European-Non Finnish (NFE) AF: 0.000491 AC: 546 AN: 1111234

Other (OTH) AF: 0.0121 AC: 729 AN: 60332

GnomAD4 genome AF: 0.0528 AC: 8010 AN: 151810 Hom.: 714 Cov.: 32 AF XY: 0.0517 AC XY: 3833 AN XY: 74190

African (AFR) AF: 0.184 AC: 7603 AN: 41316

American (AMR) AF: 0.0192 AC: 293 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10510

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

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 67984

Other (OTH) AF: 0.0348 AC: 73 AN: 2096

Alfa AF: 0.00344 Hom.: 4

Bravo AF: 0.0603

Asia WGS AF: 0.0110 AC: 40 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
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.61
PhyloP100		-1.4
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: rs13420285; hg19: chr2-101620766;