Genetic Variant NM_152719.3:c.157-8T>C (chr13-45713174-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152719.3(CBY2):c.157-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,601,310 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 6 hom. )

Consequence

CBY2
NM_152719.3 splice_region, intron

Scores

Splicing: ADA: 0.0001009

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33

Publications

0 publications found

Variant links:

Genes affected

CBY2 (HGNC:30720): (chibby family member 2) Enables identical protein binding activity. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

CBY2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-45713174-T-C is Benign according to our data. Variant chr13-45713174-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2643805.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CBY2	NM_152719.3	MANE Select	c.157-8T>C	splice_region intron	N/A	NP_689932.1	Q8NA61-1
CBY2	NM_001286341.2		c.76-8T>C	splice_region intron	N/A	NP_001273270.1
CBY2	NM_001286342.2		c.49-8T>C	splice_region intron	N/A	NP_001273271.1	Q8NA61-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CBY2	ENST00000310521.6	TSL:1 MANE Select	c.157-8T>C	splice_region intron	N/A	ENSP00000309189.1	Q8NA61-1
CBY2	ENST00000378966.3	TSL:1	c.49-8T>C	splice_region intron	N/A	ENSP00000368249.3	Q8NA61-2
CBY2	ENST00000610924.1	TSL:5	c.49-8T>C	splice_region intron	N/A	ENSP00000480148.1	Q8NA61-2

Frequencies

GnomAD3 genomes

AF:

0.000901

AC:

137

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000953

AC:

226

AN:

237226

AF XY:

0.00122

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.000328

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000520

Gnomad OTH exome

AF:

0.000515

GnomAD4 exome

AF:

0.000602

AC:

873

AN:

1449144

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

531

AN XY:

719924

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33316

American (AMR)

AF:

0.00104

AC:

AN:

44140

Ashkenazi Jewish (ASJ)

AF:

0.000237

AC:

AN:

25308

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.00413

AC:

350

AN:

84826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51788

Middle Eastern (MID)

AF:

0.00716

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.000343

AC:

379

AN:

1104646

Other (OTH)

AF:

0.000769

AC:

AN:

59830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000907

AC:

138

AN:

152166

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41526

American (AMR)

AF:

0.00419

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00458

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

68010

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000521

Hom.:

Bravo

AF:

0.000642

Asia WGS

AF:

0.00318

AC:

AN:

3478

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

-0.54

CADD

Benign

8.9

(source)

DANN

Benign

0.56

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.040

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