11-589564-T-C

Variant names:

• chr11-589564-T-C
• rs4963128
• NM_001286581.2:c.421-1820T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 108 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PHRF1	NM_001286581.2	c.421-1820T>C		intron_variant	Intron 4 of 17	ENST00000264555.10	NP_001273510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHRF1	ENST00000264555.10	c.421-1820T>C		intron_variant	Intron 4 of 17	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

African (AFR) AF: 0.541 AC: 22359 AN: 41362

American (AMR) AF: 0.670 AC: 10217 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2258 AN: 3438

East Asian (EAS) AF: 0.929 AC: 4769 AN: 5136

South Asian (SAS) AF: 0.751 AC: 3609 AN: 4806

European-Finnish (FIN) AF: 0.721 AC: 7592 AN: 10526

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.662 AC: 44896 AN: 67796

Other (OTH) AF: 0.648 AC: 1366 AN: 2108

Alfa AF: 0.662 Hom.: 127770

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
PhyloP100		-0.018
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs4963128; hg19: chr11-589564;