Genetic Variant PHRF1:c.*371T>C (chr11-612148-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001286581.2(PHRF1):c.*371T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 330,664 control chromosomes in the GnomAD database, including 10,599 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 0.27 ( 6323 hom., cov: 33)

Exomes 𝑓: 0.20 ( 4276 hom. )

Consequence

PHRF1
NM_001286581.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.532

Publications

12 publications found

Variant links:

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]

PHRF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHRF1	NM_001286581.2 link	c.*371T>C		3_prime_UTR_variant	Exon 18 of 18	ENST00000264555.10	NP_001273510.1	Q9P1Y6-1A0A024RCA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHRF1	ENST00000264555.10 link	c.*371T>C		3_prime_UTR_variant	Exon 18 of 18	1	NM_001286581.2	ENSP00000264555.5		Q9P1Y6-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40697

AN:

152138

Hom.:

6316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.0246

Gnomad SAS

AF:

0.0985

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.205

AC:

36500

AN:

178408

Hom.:

4276

Cov.:

AF XY:

0.200

AC XY:

18340

AN XY:

91870

show subpopulations

African (AFR)

AF:

0.419

AC:

2442

AN:

5824

American (AMR)

AF:

0.277

AC:

1893

AN:

6836

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

1348

AN:

6044

East Asian (EAS)

AF:

0.0212

AC:

265

AN:

12472

South Asian (SAS)

AF:

0.105

AC:

1524

AN:

14550

European-Finnish (FIN)

AF:

0.164

AC:

1588

AN:

9694

Middle Eastern (MID)

AF:

0.187

AC:

155

AN:

828

European-Non Finnish (NFE)

AF:

0.224

AC:

24904

AN:

111064

Other (OTH)

AF:

0.215

AC:

2381

AN:

11096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1368

2736

4103

5471

6839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.268

AC:

40734

AN:

152256

Hom.:

6323

Cov.:

AF XY:

0.258

AC XY:

19180

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.425

AC:

17657

AN:

41542

American (AMR)

AF:

0.261

AC:

4000

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

801

AN:

3468

East Asian (EAS)

AF:

0.0247

AC:

128

AN:

5190

South Asian (SAS)

AF:

0.0973

AC:

470

AN:

4828

European-Finnish (FIN)

AF:

0.144

AC:

1527

AN:

10610

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15369

AN:

67992

Other (OTH)

AF:

0.266

AC:

563

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1506

3011

4517

6022

7528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.256

Hom.:

1944

Bravo

AF:

0.284

Asia WGS

AF:

0.103

AC:

361

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.3

(source)

DANN

Benign

0.40

PhyloP100

-0.53

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over