rs702966

Positions:

• chr11-611919-C-G
• chr11-611919-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286581.2(PHRF1):​c.*142C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 992,038 control chromosomes in the GnomAD database, including 24,985 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 0.32 (9236 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15749 hom.)
• Consequence: PHRF1 NM_001286581.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHRF1	NM_001286581.2	c.*142C>G		3_prime_UTR_variant	18/18	ENST00000264555.10	NP_001273510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHRF1	ENST00000264555.10	c.*142C>G		3_prime_UTR_variant	18/18	1	NM_001286581.2	ENSP00000264555	P5

Frequencies

GnomAD3 genomes AF: 0.318 AC: 46860 AN: 147178 Hom.: 9220 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.130 AC: 110154 AN: 844742 Hom.: 15749 Cov.: 15 AF XY: 0.134 AC XY: 56598 AN XY: 422118

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0198

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.318 AC: 46911 AN: 147296 Hom.: 9236 Cov.: 32 AF XY: 0.307 AC XY: 22021 AN XY: 71800

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0232

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.324

Alfa AF: 0.155 Hom.: 255

Bravo AF: 0.345

Asia WGS AF: 0.0890 AC: 296 AN: 3338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.42
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		4.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs702966; hg19: chr11-611919;