12-89424245-T-G

Variant names:

• chr12-89424245-T-G
• rs770374
• NM_172240.3:c.1332+916A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 20

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

POC1B-DUSP6 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172240.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1B	NM_172240.3	MANE Select	c.1332+916A>C		intron	N/A	NP_758440.1
	POC1B	NM_001199777.2		c.1206+916A>C		intron	N/A	NP_001186706.1
	POC1B	NM_001425771.1		c.1114-19900A>C		intron	N/A	NP_001412700.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1B	ENST00000313546.8	TSL:1 MANE Select	c.1332+916A>C		intron	N/A	ENSP00000323302.3
	POC1B	ENST00000393179.8	TSL:1	c.942+916A>C		intron	N/A	ENSP00000376877.4
	POC1B	ENST00000549591.1	TSL:1	n.4300+916A>C		intron	N/A

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

African (AFR) AF: 0.664 AC: 27536 AN: 41442

American (AMR) AF: 0.546 AC: 8346 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1322 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3631 AN: 5162

South Asian (SAS) AF: 0.438 AC: 2115 AN: 4824

European-Finnish (FIN) AF: 0.422 AC: 4453 AN: 10562

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.433 AC: 29442 AN: 67932

Other (OTH) AF: 0.488 AC: 1027 AN: 2106

Alfa AF: 0.457 Hom.: 26865

Bravo AF: 0.535

Asia WGS AF: 0.544 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs770374; hg19: chr12-89818022;