11-601785-T-C

Variant names:

• chr11-601785-T-C
• rs2396545
• NM_001286581.2:c.1152+84T>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.1152+84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,557,280 control chromosomes in the GnomAD database, including 44,381 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 0.28 (7011 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37370 hom.)
• Consequence: PHRF1 NM_001286581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 22 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHRF1	NM_001286581.2	MANE Select	c.1152+84T>C		intron	N/A	NP_001273510.1
	PHRF1	NM_020901.4		c.1152+84T>C		intron	N/A	NP_065952.2
	PHRF1	NM_001286582.2		c.1149+84T>C		intron	N/A	NP_001273511.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHRF1	ENST00000264555.10	TSL:1 MANE Select	c.1152+84T>C		intron	N/A	ENSP00000264555.5
	PHRF1	ENST00000416188.3	TSL:1	c.1152+84T>C		intron	N/A	ENSP00000410626.2
	PHRF1	ENST00000413872.6	TSL:1	c.1149+84T>C		intron	N/A	ENSP00000388589.2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42257 AN: 152090 Hom.: 7001 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.222 AC: 312076 AN: 1405072 Hom.: 37370 AF XY: 0.217 AC XY: 151442 AN XY: 696908

African (AFR) AF: 0.463 AC: 14518 AN: 31338

American (AMR) AF: 0.283 AC: 10354 AN: 36632

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5221 AN: 24860

East Asian (EAS) AF: 0.0223 AC: 857 AN: 38456

South Asian (SAS) AF: 0.107 AC: 8781 AN: 81728

European-Finnish (FIN) AF: 0.157 AC: 7990 AN: 50802

Middle Eastern (MID) AF: 0.170 AC: 920 AN: 5412

European-Non Finnish (NFE) AF: 0.233 AC: 250607 AN: 1077698

Other (OTH) AF: 0.221 AC: 12828 AN: 58146

GnomAD4 genome AF: 0.278 AC: 42298 AN: 152208 Hom.: 7011 Cov.: 32 AF XY: 0.268 AC XY: 19934 AN XY: 74424

African (AFR) AF: 0.459 AC: 19051 AN: 41504

American (AMR) AF: 0.267 AC: 4090 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3466

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5186

South Asian (SAS) AF: 0.0989 AC: 478 AN: 4832

European-Finnish (FIN) AF: 0.146 AC: 1552 AN: 10614

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15415 AN: 67996

Other (OTH) AF: 0.270 AC: 570 AN: 2108

Alfa AF: 0.272 Hom.: 1040

Bravo AF: 0.297

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2396545; hg19: chr11-601785; COSMIC: COSV52762470;