Genetic Variant RIBC2:p.Asp255Asp (chr22-45426037-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_015653.5(RIBC2):c.765C>T(p.Asp255Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,614,012 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0052 ( 28 hom. )

Consequence

RIBC2
NM_015653.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.939

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 22-45426037-C-T is Benign according to our data. Variant chr22-45426037-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653287.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.939 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015653.5. 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
	RIBC2	NM_015653.5	MANE Select	c.765C>T	p.Asp255Asp	synonymous	Exon 5 of 7	NP_056468.3	Q9H4K1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIBC2	ENST00000614167.2	TSL:1 MANE Select	c.765C>T	p.Asp255Asp	synonymous	Exon 5 of 7	ENSP00000483356.1	Q9H4K1
	RIBC2	ENST00000466226.1	TSL:3	n.447C>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00414

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00566

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00448

AC:

1124

AN:

250750

AF XY:

0.00434

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00886

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00500

Gnomad NFE exome

AF:

0.00600

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00523

AC:

7640

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

3712

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33480

American (AMR)

AF:

0.00304

AC:

136

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00804

AC:

210

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00266

AC:

229

AN:

86252

European-Finnish (FIN)

AF:

0.00529

AC:

282

AN:

53334

Middle Eastern (MID)

AF:

0.00693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00575

AC:

6399

AN:

1111918

Other (OTH)

AF:

0.00523

AC:

316

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

406

811

1217

1622

2028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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:

0.00405

AC:

617

AN:

152330

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41574

American (AMR)

AF:

0.00412

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00414

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00566

AC:

385

AN:

68028

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00529

Hom.:

Bravo

AF:

0.00383

EpiCase

AF:

0.00551

EpiControl

AF:

0.00611

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

8.2

(source)

DANN

Benign

0.66

PhyloP100

0.94

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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