rs7943546

Variant names:

• chr11-612148-T-C
• rs7943546
• NM_001286581.2:c.*371T>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.*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
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.419 AC: 2442 AN: 5824

American (AMR) AF: 0.277 AC: 1893 AN: 6836

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 1348 AN: 6044

East Asian (EAS) AF: 0.0212 AC: 265 AN: 12472

South Asian (SAS) AF: 0.105 AC: 1524 AN: 14550

European-Finnish (FIN) AF: 0.164 AC: 1588 AN: 9694

Middle Eastern (MID) AF: 0.187 AC: 155 AN: 828

European-Non Finnish (NFE) AF: 0.224 AC: 24904 AN: 111064

Other (OTH) AF: 0.215 AC: 2381 AN: 11096

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

African (AFR) AF: 0.425 AC: 17657 AN: 41542

American (AMR) AF: 0.261 AC: 4000 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3468

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5190

South Asian (SAS) AF: 0.0973 AC: 470 AN: 4828

European-Finnish (FIN) AF: 0.144 AC: 1527 AN: 10610

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15369 AN: 67992

Other (OTH) AF: 0.266 AC: 563 AN: 2116

Alfa AF: 0.256 Hom.: 1944

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
PhyloP100		-0.53
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7943546; hg19: chr11-612148;