rs4687805

Positions:

• chr3-52089297-A-G

Variant summary

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

The NM_015426.5(POC1A):​c.1125+7272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,826 control chromosomes in the GnomAD database, including 6,231 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 0.26 (6231 hom., cov: 30)
• Consequence: POC1A NM_015426.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

Genes affected

POC1A (HGNC:24488): (POC1 centriolar protein A) 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. Mutations in this gene result in short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) syndrome. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POC1A	NM_015426.5	c.1125+7272T>C		intron_variant		ENST00000296484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POC1A	ENST00000296484.7	c.1125+7272T>C		intron_variant		1	NM_015426.5	P1
POC1A	ENST00000394970.6	c.982-13312T>C		intron_variant		1
POC1A	ENST00000474012.1	c.1011+7272T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39082 AN: 151708 Hom.: 6199 Cov.: 30

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.258 AC: 39174 AN: 151826 Hom.: 6231 Cov.: 30 AF XY: 0.263 AC XY: 19484 AN XY: 74200

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.228

Alfa AF: 0.183 Hom.: 1436

Bravo AF: 0.277

Asia WGS AF: 0.384 AC: 1333 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.41

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: rs4687805; hg19: chr3-52123313;