chr13-49506711-A-G

Variant names:

• chr13-49506711-A-G
• rs2031532
• NM_001040443.3:c.171A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001040443.3(PHF11):​c.171A>G​(p.Leu57Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,605,470 control chromosomes in the GnomAD database, including 369,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.73 (41321 hom., cov: 30)
  • Exomes 𝑓: 0.67 (328653 hom.)
• Consequence: PHF11 NM_001040443.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.108

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=-0.87).
• BP6: Variant 13-49506711-A-G is Benign according to our data. Variant chr13-49506711-A-G is described in ClinVar as [Benign]. Clinvar id is 3059044.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.108 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.171A>G	p.Leu57Leu	synonymous_variant	Exon 2 of 10	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.171A>G	p.Leu57Leu	synonymous_variant	Exon 2 of 10	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110659 AN: 151798 Hom.: 41259 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.705

GnomAD3 exomes AF: 0.704 AC: 176593 AN: 250890 Hom.: 63108 AF XY: 0.693 AC XY: 93990 AN XY: 135636

Gnomad AFR exome AF: 0.884

Gnomad AMR exome AF: 0.777

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.861

Gnomad SAS exome AF: 0.654

Gnomad FIN exome AF: 0.687

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.669 AC: 972541 AN: 1453554 Hom.: 328653 Cov.: 30 AF XY: 0.668 AC XY: 483382 AN XY: 723660

Gnomad4 AFR exome AF: 0.882

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.894

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.681

Gnomad4 NFE exome AF: 0.653

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.729 AC: 110780 AN: 151916 Hom.: 41321 Cov.: 30 AF XY: 0.730 AC XY: 54242 AN XY: 74260

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.702

Alfa AF: 0.663 Hom.: 57612

Bravo AF: 0.741

Asia WGS AF: 0.764 AC: 2659 AN: 3478

EpiCase AF: 0.654

EpiControl AF: 0.644

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	-0.87
CADD	Benign	0.88
DANN	Benign	0.55

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: rs2031532; hg19: chr13-50080847; COSMIC: COSV62896216;