chr12-89525072-C-T

Variant names:

• chr12-89525072-C-T
• rs75470544
• NM_172240.3:c.100+48G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.149
• Publications: 1 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-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-DUSP6 (HGNC:):

POC1B-AS1 (HGNC:52949): (POC1B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1B	NM_172240.3	MANE Select	c.100+48G>A		intron	N/A	NP_758440.1	Q8TC44-1
	POC1B-GALNT4	NM_001199781.2		c.100+48G>A		intron	N/A	NP_001186710.1	F8VUJ3
	POC1B	NM_001199777.2		c.-27+48G>A		intron	N/A	NP_001186706.1	Q8TC44-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1B	ENST00000313546.8	TSL:1 MANE Select	c.100+48G>A		intron	N/A	ENSP00000323302.3	Q8TC44-1
	POC1B-GALNT4	ENST00000548729.5	TSL:2	c.100+48G>A		intron	N/A	ENSP00000447852.1	F8VUJ3
	POC1B	ENST00000393179.8	TSL:1	c.-119+48G>A		intron	N/A	ENSP00000376877.4	Q8IU52

Frequencies

GnomAD3 genomes AF: 0.00729 AC: 1110 AN: 152180 Hom.: 13 Cov.: 33

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

GnomAD2 exomes AF: 0.00185 AC: 458 AN: 247938 AF XY: 0.00137

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 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

African (AFR) AF: 0.0226 AC: 756 AN: 33404

American (AMR) AF: 0.00180 AC: 80 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00365 AC: 21 AN: 5756

European-Non Finnish (NFE) AF: 0.000140 AC: 155 AN: 1110764

Other (OTH) AF: 0.00182 AC: 110 AN: 60284

GnomAD4 genome AF: 0.00730 AC: 1112 AN: 152298 Hom.: 13 Cov.: 33 AF XY: 0.00686 AC XY: 511 AN XY: 74454

African (AFR) AF: 0.0248 AC: 1029 AN: 41572

American (AMR) AF: 0.00366 AC: 56 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68022

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00458 Hom.: 2

Bravo AF: 0.00839

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.59
PhyloP100		-0.15
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs75470544; hg19: chr12-89918849;