rs4687805

Variant names:

• chr3-52089297-A-G
• rs4687805
• NM_015426.5:c.1125+7272T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

POC1A Gene-Disease associations (from GenCC):

• short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POC1A	NM_015426.5	c.1125+7272T>C		intron_variant	Intron 10 of 10	ENST00000296484.7	NP_056241.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POC1A	ENST00000296484.7	c.1125+7272T>C		intron_variant	Intron 10 of 10	1	NM_015426.5	ENSP00000296484.2
POC1A	ENST00000394970.6	c.982-13312T>C		intron_variant	Intron 9 of 9	1		ENSP00000378421.2
POC1A	ENST00000474012.1	c.1011+7272T>C		intron_variant	Intron 10 of 10	2		ENSP00000418968.1

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

African (AFR) AF: 0.405 AC: 16727 AN: 41352

American (AMR) AF: 0.332 AC: 5062 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2311 AN: 5138

South Asian (SAS) AF: 0.239 AC: 1147 AN: 4804

European-Finnish (FIN) AF: 0.216 AC: 2281 AN: 10542

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10462 AN: 67948

Other (OTH) AF: 0.228 AC: 482 AN: 2110

Alfa AF: 0.182 Hom.: 1582

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
PhyloP100		1.1
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: rs4687805; hg19: chr3-52123313;