dbSNP rs2278723: RPL31:c.107+51T>C (chr2-101002859-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.116

Publications

8 publications found

Variant links:

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

RPL31 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 1246390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL31	NM_000993.5	MANE Select	c.107+51T>C	intron	N/A	NP_000984.1	P62899-1
RPL31	NM_001098577.3		c.107+51T>C	intron	N/A	NP_001092047.1	P62899-2
RPL31	NM_001099693.2		c.107+51T>C	intron	N/A	NP_001093163.1	P62899-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL31	ENST00000264258.8	TSL:1 MANE Select	c.107+51T>C	intron	N/A	ENSP00000264258.3	P62899-1
RPL31	ENST00000409733.5	TSL:1	c.107+51T>C	intron	N/A	ENSP00000386681.1	P62899-1
RPL31	ENST00000409320.7	TSL:1	c.107+51T>C	intron	N/A	ENSP00000387163.3	P62899-3

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94391

AN:

151804

Hom.:

29915

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.614

AC:

148973

AN:

242492

AF XY:

0.619

show subpopulations

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 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.:

AF XY:

0.652

AC XY:

400158

AN XY:

613798

show subpopulations

African (AFR)

AF:

0.565

AC:

16080

AN:

28468

American (AMR)

AF:

0.566

AC:

24555

AN:

43370

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

18269

AN:

24404

East Asian (EAS)

AF:

0.360

AC:

13807

AN:

38344

South Asian (SAS)

AF:

0.584

AC:

47394

AN:

81172

European-Finnish (FIN)

AF:

0.596

AC:

31584

AN:

52974

Middle Eastern (MID)

AF:

0.694

AC:

3670

AN:

5292

European-Non Finnish (NFE)

AF:

0.680

AC:

602396

AN:

885668

Other (OTH)

AF:

0.634

AC:

32938

AN:

51958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13228

26455

39683

52910

66138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13920

27840

41760

55680

69600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.622

AC:

94441

AN:

151924

Hom.:

29926

Cov.:

AF XY:

0.617

AC XY:

45765

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.562

AC:

23247

AN:

41396

American (AMR)

AF:

0.602

AC:

9199

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

2571

AN:

3472

East Asian (EAS)

AF:

0.338

AC:

1741

AN:

5154

South Asian (SAS)

AF:

0.590

AC:

2831

AN:

4798

European-Finnish (FIN)

AF:

0.595

AC:

6269

AN:

10544

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.683

AC:

46406

AN:

67966

Other (OTH)

AF:

0.642

AC:

1355

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1707

3414

5122

6829

8536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.662

Hom.:

31245

Bravo

AF:

0.619

Asia WGS

AF:

0.462

AC:

1612

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.9

(source)

DANN

Benign

0.74

PhyloP100

-0.12

PromoterAI

-0.077

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over