11-612355-T-C

Variant names:

• chr11-612355-T-C
• rs12805435
• NM_001286581.2:c.*578T>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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 19 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]

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)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHRF1	NM_001286581.2	MANE Select	c.*578T>C		downstream_gene	N/A	NP_001273510.1	Q9P1Y6-1
	IRF7	NM_001572.5	MANE Select	c.*290A>G		downstream_gene	N/A	NP_001563.2
	PHRF1	NM_020901.4		c.*578T>C		downstream_gene	N/A	NP_065952.2	Q9P1Y6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHRF1	ENST00000264555.10	TSL:1 MANE Select	c.*578T>C		downstream_gene	N/A	ENSP00000264555.5	Q9P1Y6-1
	IRF7	ENST00000525445.6	TSL:5 MANE Select	c.*290A>G		downstream_gene	N/A	ENSP00000434009.2	Q92985-1
	IRF7	ENST00000397566.5	TSL:1	c.*290A>G		downstream_gene	N/A	ENSP00000380697.1	Q92985-4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49422 AN: 152054 Hom.: 9401 Cov.: 34

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

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

GnomAD4 genome AF: 0.325 AC: 49473 AN: 152172 Hom.: 9417 Cov.: 34 AF XY: 0.314 AC XY: 23369 AN XY: 74398

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.97

Splicing

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

Other links and lift over

dbSNP: rs12805435; hg19: chr11-612355;