NM_172240.3:c.101-6269G>A

Variant names:

• chr12-89503611-C-T
• rs11105306
• NM_172240.3:c.101-6269G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172240.3(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 NM_172240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 12 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=-0.91).
• 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 rank	MANE	Protein	UniProt
POC1B	NM_172240.3	c.101-6269G>A		intron_variant	Intron 2 of 11	ENST00000313546.8	NP_758440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POC1B	ENST00000313546.8	c.101-6269G>A		intron_variant	Intron 2 of 11	1	NM_172240.3	ENSP00000323302.3

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

African (AFR) AF: 0.105 AC: 4237 AN: 40518

American (AMR) AF: 0.173 AC: 2559 AN: 14818

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 859 AN: 3378

East Asian (EAS) AF: 0.165 AC: 799 AN: 4842

South Asian (SAS) AF: 0.348 AC: 1567 AN: 4502

European-Finnish (FIN) AF: 0.208 AC: 2121 AN: 10212

Middle Eastern (MID) AF: 0.239 AC: 66 AN: 276

European-Non Finnish (NFE) AF: 0.223 AC: 14674 AN: 65822

Other (OTH) AF: 0.194 AC: 398 AN: 2048

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
PhyloP100		0.055
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: rs11105306; hg19: chr12-89897388;