Genetic Variant CEP170B:p.Pro198Pro (chr14-104883051-A-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001112726.3(CEP170B):c.594A>T(p.Pro198Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 151,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P198P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP170B
NM_001112726.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Publications

28 publications found

Variant links:

Genes affected

CEP170B (HGNC:20362): (centrosomal protein 170B) Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CEP170B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP7

Synonymous conserved (PhyloP=-1.84 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170B	NM_001112726.3 link	c.594A>T	p.Pro198Pro	synonymous_variant	Exon 8 of 19	ENST00000414716.8	NP_001106197.1	Q9Y4F5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP170B	ENST00000414716.8 link	c.594A>T	p.Pro198Pro	synonymous_variant	Exon 8 of 19	1	NM_001112726.3	ENSP00000404151.2		Q9Y4F5-2
CEP170B	ENST00000556508.5 link	c.384A>T	p.Pro128Pro	synonymous_variant	Exon 7 of 18	5		ENSP00000451249.1		Q9Y4F5-3

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000483

GnomAD2 exomes

AF:

0.0000136

AC:

AN:

146532

AF XY:

0.0000250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000402

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000725

AC:

AN:

1378382

Hom.:

Cov.:

AF XY:

0.00000884

AC XY:

AN XY:

678364

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31526

American (AMR)

AF:

0.0000280

AC:

AN:

35678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24138

East Asian (EAS)

AF:

0.00

AC:

AN:

36390

South Asian (SAS)

AF:

0.00

AC:

AN:

78462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.00000653

AC:

AN:

1072124

Other (OTH)

AF:

0.0000175

AC:

AN:

57292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000397

AC:

AN:

151256

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

73850

show subpopulations

African (AFR)

AF:

0.0000729

AC:

AN:

41164

American (AMR)

AF:

0.0000657

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67730

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

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:

0.00

Hom.:

103932

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.41

(source)

DANN

Benign

0.56

PhyloP100

-1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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