chr12-89525072-C-T

Variant summary

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

The NM_172240.3(POC1B):​c.100+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,612,180 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 13 hom., cov: 33)
Exomes 𝑓: 0.00077 ( 10 hom. )

Consequence

POC1B
NM_172240.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.149
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-GALNT4 (HGNC:42957): (POC1B-GALNT4 readthrough) This locus represents naturally occurring transcripts that splice the 5' exons of the POC1B (POC1 centriolar protein homolog B) gene on chromosome 12 to the GALNT4 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4) gene, which is located within a POC1B intron. Alternative splicing results in two transcript variants, one of which encodes a fusion isoform that shares sequence identity with the products of each individual gene. [provided by RefSeq, Dec 2010]
POC1B-AS1 (HGNC:52949): (POC1B antisense RNA 1)

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 (BayesDel_noAF=-0.77).
BP6
Variant 12-89525072-C-T is Benign according to our data. Variant chr12-89525072-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1210501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0073 (1112/152298) while in subpopulation AFR AF= 0.0248 (1029/41572). AF 95% confidence interval is 0.0235. There are 13 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POC1BNM_172240.3 linkc.100+48G>A intron_variant Intron 2 of 11 ENST00000313546.8 NP_758440.1 Q8TC44-1A0MNP0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POC1BENST00000313546.8 linkc.100+48G>A intron_variant Intron 2 of 11 1 NM_172240.3 ENSP00000323302.3 Q8TC44-1
POC1B-GALNT4ENST00000548729.5 linkc.100+48G>A intron_variant Intron 2 of 2 2 ENSP00000447852.1 F8VUJ3

Frequencies

GnomAD3 genomes
AF:
0.00729
AC:
1110
AN:
152180
Hom.:
13
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0248
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00366
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:
0.000250
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.00185
AC:
458
AN:
247938
Hom.:
3
AF XY:
0.00137
AC XY:
184
AN XY:
134338
show subpopulations
Gnomad AFR exome
AF:
0.0235
Gnomad AMR exome
AF:
0.00178
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:
0.000188
Gnomad OTH exome
AF:
0.00132
GnomAD4 exome
AF:
0.000773
AC:
1129
AN:
1459882
Hom.:
10
Cov.:
29
AF XY:
0.000662
AC XY:
481
AN XY:
726220
show subpopulations
Gnomad4 AFR exome
AF:
0.0226
Gnomad4 AMR exome
AF:
0.00180
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000697
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000140
Gnomad4 OTH exome
AF:
0.00182
GnomAD4 genome
AF:
0.00730
AC:
1112
AN:
152298
Hom.:
13
Cov.:
33
AF XY:
0.00686
AC XY:
511
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0248
Gnomad4 AMR
AF:
0.00366
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00589
Hom.:
1
Bravo
AF:
0.00839
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Feb 02, 2019
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
6.9
DANN
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

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

Other links and lift over

dbSNP: rs75470544; hg19: chr12-89918849; API