rs72821045

Variant names:

• chr2-101002915-C-T
• rs72821045
• NM_000993.5:c.107+107C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-101002915-C-T
• chr2-101002915-C-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+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
• Publications: 1 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=-0.79).
• BP6: Variant 2-101002915-C-T is Benign according to our data. Variant chr2-101002915-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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+107C>T		intron	N/A	NP_000984.1	P62899-1
	RPL31	NM_001098577.3		c.107+107C>T		intron	N/A	NP_001092047.1	P62899-2
	RPL31	NM_001099693.2		c.107+107C>T		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+107C>T		intron	N/A	ENSP00000264258.3	P62899-1
	RPL31	ENST00000409733.5	TSL:1	c.107+107C>T		intron	N/A	ENSP00000386681.1	P62899-1
	RPL31	ENST00000409320.7	TSL:1	c.107+107C>T		intron	N/A	ENSP00000387163.3	P62899-3

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

African (AFR) AF: 0.0503 AC: 818 AN: 16262

American (AMR) AF: 0.0738 AC: 2108 AN: 28550

Ashkenazi Jewish (ASJ) AF: 0.0595 AC: 1022 AN: 17166

East Asian (EAS) AF: 0.000539 AC: 18 AN: 33414

South Asian (SAS) AF: 0.0757 AC: 4515 AN: 59658

European-Finnish (FIN) AF: 0.153 AC: 7316 AN: 47780

Middle Eastern (MID) AF: 0.0632 AC: 254 AN: 4016

European-Non Finnish (NFE) AF: 0.142 AC: 55608 AN: 390690

Other (OTH) AF: 0.107 AC: 3477 AN: 32410

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

African (AFR) AF: 0.0523 AC: 2171 AN: 41512

American (AMR) AF: 0.0965 AC: 1475 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1625 AN: 10568

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9480 AN: 67982

Other (OTH) AF: 0.104 AC: 219 AN: 2108

Alfa AF: 0.0533 Hom.: 54

Bravo AF: 0.0973

Asia WGS AF: 0.0300 AC: 107 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	-0.79
CADD	Benign	8.6
DANN	Benign	0.71
PhyloP100		0.11
PromoterAI		0.018	Neutral
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: rs72821045; hg19: chr2-101619377;