Genetic Variant RIBC2:p.Leu245Leu (chr22-45426007-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015653.5(RIBC2):c.735G>A(p.Leu245Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,612,828 control chromosomes in the GnomAD database, including 226,601 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 31191 hom., cov: 33)

Exomes 𝑓: 0.51 ( 195410 hom. )

Consequence

RIBC2
NM_015653.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.76

Publications

37 publications found

Variant links:

Genes affected

RIBC2 (HGNC:13241): (RIB43A domain with coiled-coils 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RIBC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=2.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIBC2	NM_015653.5 link	c.735G>A	p.Leu245Leu	synonymous_variant	Exon 5 of 7	ENST00000614167.2	NP_056468.3	Q9H4K1
RIBC2	XM_005261524.5 link	c.516G>A	p.Leu172Leu	synonymous_variant	Exon 5 of 7		XP_005261581.1	Q9H4K1
RIBC2	XM_011530126.3 link	c.246G>A	p.Leu82Leu	synonymous_variant	Exon 3 of 5		XP_011528428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIBC2	ENST00000614167.2 link	c.735G>A	p.Leu245Leu	synonymous_variant	Exon 5 of 7	1	NM_015653.5	ENSP00000483356.1		Q9H4K1
RIBC2	ENST00000466226.1 link	n.417G>A		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.616

AC:

93632

AN:

151970

Hom.:

31143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.614

GnomAD2 exomes

AF:

0.563

AC:

140851

AN:

250128

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.883

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.704

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.489

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.509

AC:

743789

AN:

1460740

Hom.:

195410

Cov.:

AF XY:

0.512

AC XY:

372235

AN XY:

726610

show subpopulations

African (AFR)

AF:

0.890

AC:

29803

AN:

33474

American (AMR)

AF:

0.534

AC:

23799

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

14497

AN:

26130

East Asian (EAS)

AF:

0.631

AC:

25046

AN:

39686

South Asian (SAS)

AF:

0.667

AC:

57475

AN:

86226

European-Finnish (FIN)

AF:

0.492

AC:

26209

AN:

53282

Middle Eastern (MID)

AF:

0.634

AC:

3656

AN:

5768

European-Non Finnish (NFE)

AF:

0.477

AC:

529954

AN:

1111226

Other (OTH)

AF:

0.552

AC:

33350

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

20543

41086

61628

82171

102714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15874

31748

47622

63496

79370

<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:

0.616

AC:

93740

AN:

152088

Hom.:

31191

Cov.:

AF XY:

0.619

AC XY:

46047

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.875

AC:

36323

AN:

41524

American (AMR)

AF:

0.574

AC:

8780

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

1928

AN:

3466

East Asian (EAS)

AF:

0.682

AC:

3514

AN:

5156

South Asian (SAS)

AF:

0.685

AC:

3303

AN:

4824

European-Finnish (FIN)

AF:

0.503

AC:

5316

AN:

10578

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32567

AN:

67946

Other (OTH)

AF:

0.618

AC:

1302

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1634

3268

4901

6535

8169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.543

Hom.:

60770

Bravo

AF:

0.631

Asia WGS

AF:

0.751

AC:

2613

AN:

3478

EpiCase

AF:

0.497

EpiControl

AF:

0.516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.6

(source)

DANN

Benign

0.62

PhyloP100

2.8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over