11-589564-T-C

Position:

• chr11-589564-T-C

Variant summary

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

The NM_001286581.2(PHRF1):​c.421-1820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,592 control chromosomes in the GnomAD database, including 32,046 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 0.65 (32046 hom., cov: 34)
• Consequence: PHRF1 NM_001286581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

Genes affected

PHRF1 (HGNC:24351): (PHD and ring finger domains 1) Predicted to enable RNA polymerase binding activity. Predicted to be involved in mRNA processing and transcription by RNA polymerase II. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHRF1	NM_001286581.2	c.421-1820T>C		intron_variant		ENST00000264555.10	NP_001273510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHRF1	ENST00000264555.10	c.421-1820T>C		intron_variant		1	NM_001286581.2	ENSP00000264555.5

Frequencies

GnomAD3 genomes AF: 0.646 AC: 97821 AN: 151474 Hom.: 32025 Cov.: 34

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.646 AC: 97889 AN: 151592 Hom.: 32046 Cov.: 34 AF XY: 0.653 AC XY: 48375 AN XY: 74070

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.648

Alfa AF: 0.666 Hom.: 62356

Bravo AF: 0.640

Asia WGS AF: 0.812 AC: 2824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4963128; hg19: chr11-589564;