rs1046295

chr13-49528674-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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 (★).

• 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 criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
PHF11	NM_001040443.3	c.*9G>A		3_prime_UTR_variant	10/10	ENST00000378319.8
SETDB2-PHF11	NR_135324.2	n.3616G>A		non_coding_transcript_exon_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF11	ENST00000378319.8	c.*9G>A		3_prime_UTR_variant	10/10	1	NM_001040443.3	P2

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

GnomAD3 exomes AF: 0.496 AC: 112360 AN: 226708 Hom.: 28392 AF XY: 0.491 AC XY: 60336 AN XY: 122778

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 SAS exome AF: 0.319

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

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.511

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

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.503

Alfa AF: 0.524 Hom.: 22368

Bravo AF: 0.476

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PHF11-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1046295; hg19: chr13-50102810; COSMIC: COSV51633661; COSMIC: COSV51633661;