chr12-89421240-C-T

Variant names:

• chr12-89421240-C-T
• rs2120630653
• NM_172240.3:c.1350G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_172240.3(POC1B):​c.1350G>A​(p.Glu450Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POC1B NM_172240.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.84
• Publications: 0 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 12-89421240-C-T is Benign according to our data. Variant chr12-89421240-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1561206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.

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.1350G>A	p.Glu450Glu	synonymous	Exon 12 of 12	NP_758440.1	Q8TC44-1
	POC1B	NM_001199777.2		c.1224G>A	p.Glu408Glu	synonymous	Exon 11 of 11	NP_001186706.1	Q8TC44-2
	POC1B	NM_001425771.1		c.1114-16895G>A		intron	N/A	NP_001412700.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1B	ENST00000313546.8	TSL:1 MANE Select	c.1350G>A	p.Glu450Glu	synonymous	Exon 12 of 12	ENSP00000323302.3	Q8TC44-1
	POC1B	ENST00000393179.8	TSL:1	c.960G>A	p.Glu320Glu	synonymous	Exon 10 of 10	ENSP00000376877.4	Q8IU52
	POC1B	ENST00000549591.1	TSL:1	n.4318G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444400 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716426

African (AFR) AF: 0.00 AC: 0 AN: 33312

American (AMR) AF: 0.00 AC: 0 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25624

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.00 AC: 0 AN: 84578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099128

Other (OTH) AF: 0.00 AC: 0 AN: 59554

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		1.8

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: rs2120630653; hg19: chr12-89815017;