12-89503611-C-T

Position:

• chr12-89503611-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000313546.8(POC1B):​c.101-6269G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 147,308 control chromosomes in the GnomAD database, including 3,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3043 hom., cov: 30)
• Consequence: POC1B ENST00000313546.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POC1B	NM_172240.3	c.101-6269G>A		intron_variant		ENST00000313546.8	NP_758440.1
POC1B	NM_001199777.2	c.-26-6269G>A		intron_variant			NP_001186706.1
POC1B	NR_037659.2	n.253-11496G>A		intron_variant, non_coding_transcript_variant
POC1B	NR_037660.2	n.312-11496G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POC1B	ENST00000313546.8	c.101-6269G>A		intron_variant		1	NM_172240.3	ENSP00000323302	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 27354 AN: 147174 Hom.: 3040 Cov.: 30

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0964

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.230

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 27366 AN: 147308 Hom.: 3043 Cov.: 30 AF XY: 0.188 AC XY: 13567 AN XY: 71996

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.194

Alfa AF: 0.182 Hom.: 269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs11105306; hg19: chr12-89897388;