chr11-612182-T-C

Variant names:

• chr11-612182-T-C
• rs1055382
• NM_001286581.2:c.*405T>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.*405T>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 0.286 in 306,236 control chromosomes in the GnomAD database, including 15,057 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 (9411 hom., cov: 34)
  • Exomes 𝑓: 0.25 (5646 hom.)
• Consequence: PHRF1 NM_001286581.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 10 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=-0.94).
• 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.*405T>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.*405T>C		3_prime_UTR_variant	Exon 18 of 18	1	NM_001286581.2	ENSP00000264555.5

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49419 AN: 152118 Hom.: 9395 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: 0.0256

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.247 AC: 38090 AN: 154000 Hom.: 5646 Cov.: 0 AF XY: 0.242 AC XY: 19118 AN XY: 79072

African (AFR) AF: 0.513 AC: 2742 AN: 5342

American (AMR) AF: 0.315 AC: 1953 AN: 6200

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1663 AN: 5094

East Asian (EAS) AF: 0.0226 AC: 239 AN: 10580

South Asian (SAS) AF: 0.133 AC: 1725 AN: 12944

European-Finnish (FIN) AF: 0.206 AC: 1639 AN: 7944

Middle Eastern (MID) AF: 0.280 AC: 194 AN: 694

European-Non Finnish (NFE) AF: 0.265 AC: 25379 AN: 95804

Other (OTH) AF: 0.272 AC: 2556 AN: 9398

GnomAD4 genome AF: 0.325 AC: 49470 AN: 152236 Hom.: 9411 Cov.: 34 AF XY: 0.314 AC XY: 23377 AN XY: 74440

African (AFR) AF: 0.518 AC: 21529 AN: 41526

American (AMR) AF: 0.307 AC: 4691 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.0256 AC: 133 AN: 5190

South Asian (SAS) AF: 0.127 AC: 616 AN: 4832

European-Finnish (FIN) AF: 0.185 AC: 1960 AN: 10600

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18352 AN: 68004

Other (OTH) AF: 0.330 AC: 697 AN: 2114

Alfa AF: 0.308 Hom.: 4785

Bravo AF: 0.345

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	-0.94
CADD	Benign	0.81
DANN	Benign	0.38
PhyloP100		-2.6
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: rs1055382; hg19: chr11-612182;