Genetic Variant PHRF1:c.*578T>C (chr11-612355-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

-12

BP4_StrongBA1

The NM_001286581.2(PHRF1):c.*578T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 515,928 control chromosomes in the GnomAD database, including 22,124 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 0.33 ( 9417 hom., cov: 34)

Exomes 𝑓: 0.24 ( 12707 hom. )

Consequence

PHRF1
NM_001286581.2 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.975

Publications

19 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:

IRF7 (HGNC:6122): (interferon regulatory factor 7) This gene encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. It has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue. The encoded protein plays an important role in the innate immune response against DNA and RNA viruses. [provided by RefSeq, Jul 2021]

IRF7 Gene-Disease associations (from GenCC):

immunodeficiency 39
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

IRF7 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHRF1	NM_001286581.2 link	c.*578T>C		downstream_gene_variant		ENST00000264555.10	NP_001273510.1	Q9P1Y6-1A0A024RCA1
IRF7	NM_001572.5 link	c.*290A>G		downstream_gene_variant		ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHRF1	ENST00000264555.10 link	c.*578T>C		downstream_gene_variant		1	NM_001286581.2	ENSP00000264555.5		Q9P1Y6-1
IRF7	ENST00000525445.6 link	c.*290A>G		downstream_gene_variant		5	NM_001572.5	ENSP00000434009.2		Q92985-1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49422

AN:

152054

Hom.:

9401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0255

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.331

GnomAD4 exome

AF:

0.243

AC:

88573

AN:

363756

Hom.:

12707

AF XY:

0.237

AC XY:

44950

AN XY:

189322

show subpopulations

African (AFR)

AF:

0.515

AC:

5654

AN:

10988

American (AMR)

AF:

0.307

AC:

4433

AN:

14452

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

3847

AN:

11700

East Asian (EAS)

AF:

0.0213

AC:

565

AN:

26484

South Asian (SAS)

AF:

0.134

AC:

4526

AN:

33774

European-Finnish (FIN)

AF:

0.201

AC:

4711

AN:

23462

Middle Eastern (MID)

AF:

0.297

AC:

493

AN:

1660

European-Non Finnish (NFE)

AF:

0.267

AC:

58526

AN:

219540

Other (OTH)

AF:

0.268

AC:

5818

AN:

21696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3003

6006

9008

12011

15014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.325

AC:

49473

AN:

152172

Hom.:

9417

Cov.:

AF XY:

0.314

AC XY:

23369

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.519

AC:

21531

AN:

41522

American (AMR)

AF:

0.307

AC:

4685

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3470

East Asian (EAS)

AF:

0.0255

AC:

132

AN:

5174

South Asian (SAS)

AF:

0.127

AC:

612

AN:

4824

European-Finnish (FIN)

AF:

0.185

AC:

1962

AN:

10616

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18362

AN:

67968

Other (OTH)

AF:

0.330

AC:

696

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1629

3258

4887

6516

8145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.281

Hom.:

7175

Bravo

AF:

0.346

Asia WGS

AF:

0.126

AC:

439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.3

(source)

DANN

Benign

0.61

PhyloP100

-0.97

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