rs1046295

Variant names:

• chr13-49528674-G-A
• rs1046295
• ENST00000465045.5:n.*372G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001040443.3(PHF11):​c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,573,548 control chromosomes in the GnomAD database, including 209,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.48 (17652 hom., cov: 32)
  • Exomes 𝑓: 0.52 (192163 hom.)
• Consequence: PHF11 NM_001040443.3 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.28
• Publications: 34 publications found

Genes affected

PHF11 (HGNC:17024): (PHD finger protein 11) This gene encodes a protein containing a PHD (plant homeodomain) type zinc finger. This gene has been identified in some studies as a candidate gene for asthma. Naturally-occurring readthrough transcription may occur from the upstream SETDB2 (SET domain bifurcated 2) gene to this locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

SETDB2-PHF11 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-49528674-G-A is Benign according to our data. Variant chr13-49528674-G-A is described in ClinVar as [Benign]. Clinvar id is 3059533.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.*9G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.*9G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72294 AN: 151872 Hom.: 17641 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.506

GnomAD2 exomes AF: 0.496 AC: 112360 AN: 226708 AF XY: 0.491

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.533

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.534

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.515 AC: 732671 AN: 1421560 Hom.: 192163 Cov.: 26 AF XY: 0.511 AC XY: 361893 AN XY: 707694

African (AFR) AF: 0.360 AC: 11456 AN: 31816

American (AMR) AF: 0.523 AC: 19867 AN: 38016

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 13967 AN: 24724

East Asian (EAS) AF: 0.492 AC: 19384 AN: 39428

South Asian (SAS) AF: 0.316 AC: 25618 AN: 81118

European-Finnish (FIN) AF: 0.535 AC: 27550 AN: 51448

Middle Eastern (MID) AF: 0.539 AC: 3024 AN: 5614

European-Non Finnish (NFE) AF: 0.533 AC: 581728 AN: 1090546

Other (OTH) AF: 0.511 AC: 30077 AN: 58850

GnomAD4 genome AF: 0.476 AC: 72339 AN: 151988 Hom.: 17652 Cov.: 32 AF XY: 0.473 AC XY: 35114 AN XY: 74276

African (AFR) AF: 0.365 AC: 15138 AN: 41448

American (AMR) AF: 0.521 AC: 7966 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2416 AN: 5164

South Asian (SAS) AF: 0.319 AC: 1533 AN: 4800

European-Finnish (FIN) AF: 0.528 AC: 5563 AN: 10528

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36213 AN: 67978

Other (OTH) AF: 0.503 AC: 1064 AN: 2116

Alfa AF: 0.519 Hom.: 28321

Bravo AF: 0.476

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PHF11-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.58
DANN	Benign	0.56
PhyloP100		-1.3
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: rs1046295; hg19: chr13-50102810; COSMIC: COSV51633661; COSMIC: COSV51633661;