12-89424245-T-G

Variant summary

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

The NM_172240.3(POC1B):c.1332+916A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,978 control chromosomes in the GnomAD database, including 21,233 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 0.52 (21233 hom., cov: 31)
• Consequence: POC1B NM_172240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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]

LOC124902981 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POC1B	NM_172240.3	c.1332+916A>C		intron_variant		ENST00000313546.8
LOC124902981	XR_007063401.1	n.527-461T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POC1B	ENST00000313546.8	c.1332+916A>C		intron_variant		1	NM_172240.3	P1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78396 AN: 151860 Hom.: 21202 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.516 AC: 78481 AN: 151978 Hom.: 21233 Cov.: 31 AF XY: 0.516 AC XY: 38312 AN XY: 74288

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.488

Alfa AF: 0.449 Hom.: 20341

Bravo AF: 0.535

Asia WGS AF: 0.544 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.2
Dann	Benign	0.64

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: rs770374; hg19: chr12-89818022;