11-612355-T-C

Variant names:

• chr11-612355-T-C
• rs12805435
• NM_001286581.2:c.*578T>C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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	c.*578T>C		downstream_gene_variant		ENST00000264555.10	NP_001273510.1
IRF7	NM_001572.5	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	c.*578T>C		downstream_gene_variant		1	NM_001286581.2	ENSP00000264555.5
IRF7	ENST00000525445.6	c.*290A>G		downstream_gene_variant		5	NM_001572.5	ENSP00000434009.2

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

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.0213

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.268

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

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.330

Alfa AF: 0.275 Hom.: 5735

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
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12805435; hg19: chr11-612355;