12-8930259-A-G

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.613-176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,216 control chromosomes in the GnomAD database, including 57,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.86 (57608 hom., cov: 32)
• Consequence: PHC1 NM_004426.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.368

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=-0.95).
• BP6: Variant 12-8930259-A-G is Benign according to our data. Variant chr12-8930259-A-G is described in ClinVar as [Benign]. Clinvar id is 1280679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHC1	NM_004426.3	c.613-176A>G		intron_variant		ENST00000544916.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHC1	ENST00000544916.6	c.613-176A>G		intron_variant		1	NM_004426.3	P1

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130904 AN: 152098 Hom.: 57582 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.949

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.860 AC: 130976 AN: 152216 Hom.: 57608 Cov.: 32 AF XY: 0.861 AC XY: 64096 AN XY: 74442

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.970

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.863

Alfa AF: 0.901 Hom.: 7780

Bravo AF: 0.845

Asia WGS AF: 0.880 AC: 3059 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	7.8
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1805778; hg19: chr12-9082855;