rs7943546

Variant names:

• chr11-612148-T-C
• rs7943546
• NM_001286581.2:c.*371T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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=-0.95).
• 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	c.*371T>C		3_prime_UTR_variant	Exon 18 of 18	ENST00000264555.10	NP_001273510.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40697 AN: 152138 Hom.: 6316 Cov.: 33

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.: 0 AF XY: 0.200 AC XY: 18340 AN XY: 91870

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.0212

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.268 AC: 40734 AN: 152256 Hom.: 6323 Cov.: 33 AF XY: 0.258 AC XY: 19180 AN XY: 74454

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.0973

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.266

Alfa AF: 0.262 Hom.: 1232

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
DANN	Benign	0.40
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7943546; hg19: chr11-612148;