rs1805733

Positions:

• chr12-8936676-A-C
• chr12-8936676-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004426.3(PHC1):​c.2369-180A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,964 control chromosomes in the GnomAD database, including 11,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11465 hom., cov: 31)
• Consequence: PHC1 NM_004426.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.77

Genes affected

PHC1 (HGNC:3182): (polyhomeotic homolog 1) This gene is a homolog of the Drosophila polyhomeotic gene, which is a member of the Polycomb group of genes. The gene product is a component of a multimeric protein complex that contains EDR2 and the vertebrate Polycomb protein BMH1. The gene product, the EDR2 protein, and the Drosophila polyhomeotic protein share 2 highly conserved domains, named homology domains I and II. These domains are involved in protein-protein interactions and may mediate heterodimerization of the protein encoded by this gene and the EDR2 protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-8936676-A-C is Benign according to our data. Variant chr12-8936676-A-C is described in ClinVar as [Benign]. Clinvar id is 1227373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHC1	NM_004426.3	c.2369-180A>C		intron_variant		ENST00000544916.6	NP_004417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHC1	ENST00000544916.6	c.2369-180A>C		intron_variant		1	NM_004426.3	ENSP00000437659.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56309 AN: 151846 Hom.: 11459 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.371 AC: 56325 AN: 151964 Hom.: 11465 Cov.: 31 AF XY: 0.374 AC XY: 27733 AN XY: 74250

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.386

Alfa AF: 0.404 Hom.: 7404

Bravo AF: 0.357

Asia WGS AF: 0.420 AC: 1463 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.56

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: rs1805733; hg19: chr12-9089272;