12-89421157-C-A

Position:

chr12-89421157-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_172240.3(POC1B):c.1433G>T(p.Ser478Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,582,182 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S478N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

POC1B
NM_172240.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.370

Variant links:

Genes affected

POC1B (HGNC:30836): (POC1 centriolar protein B) POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutation in this gene result in autosomal-recessive cone-rod dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

POC1B links:

POC1B (HGNC:):

POC1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051628053).

BP6

Variant 12-89421157-C-A is Benign according to our data. Variant chr12-89421157-C-A is described in ClinVar as [Benign]. Clinvar id is 733918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-89421157-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00287 (437/152276) while in subpopulation AFR AF= 0.00996 (414/41558). AF 95% confidence interval is 0.00917. There are 2 homozygotes in gnomad4. There are 204 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POC1B	NM_172240.3 linkuse as main transcript	c.1433G>T	p.Ser478Ile	missense_variant	12/12	ENST00000313546.8	NP_758440.1	Q8TC44-1A0MNP0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POC1B	ENST00000313546.8 linkuse as main transcript	c.1433G>T	p.Ser478Ile	missense_variant	12/12	1	NM_172240.3	ENSP00000323302.3		Q8TC44-1

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

432

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00987

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000811

AC:

193

AN:

238120

Hom.:

AF XY:

0.000599

AC XY:

AN XY:

128482

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.000801

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000944

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.000307

AC:

439

AN:

1429906

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

179

AN XY:

705774

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.000730

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000175

Gnomad4 OTH exome

AF:

0.000798

GnomAD4 genome

AF:

0.00287

AC:

437

AN:

152276

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00996

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000373

Hom.:

Bravo

AF:

0.00354

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000989

AC:

120

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

POC1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

.;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.058

Sift

Uncertain

0.0020

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0

.;B;.

Vest4

0.087

MVP

0.52

MPC

0.12

ClinPred

0.036

GERP RS

2.1

Varity_R

0.13

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over