rs2031532

Variant names:

• chr13-49506711-A-G
• rs2031532
• NM_001040443.3:c.171A>G
• PHF11 p.Leu57Leu

Your query was ambiguous. Multiple possible variants found:

• chr13-49506711-A-G
• chr13-49506711-A-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 47 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040443.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF11	NM_001040443.3	MANE Select	c.171A>G	p.Leu57Leu	synonymous	Exon 2 of 10	NP_001035533.1	Q9UIL8-1
	SETDB2-PHF11	NM_001320727.2		c.1653A>G	p.Leu551Leu	synonymous	Exon 12 of 20	NP_001307656.1
	PHF11	NM_001040444.3		c.54A>G	p.Leu18Leu	synonymous	Exon 3 of 11	NP_001035534.1	Q9UIL8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF11	ENST00000378319.8	TSL:1 MANE Select	c.171A>G	p.Leu57Leu	synonymous	Exon 2 of 10	ENSP00000367570.3	Q9UIL8-1
	PHF11	ENST00000488958.5	TSL:1	c.54A>G	p.Leu18Leu	synonymous	Exon 2 of 10	ENSP00000417539.1	Q9UIL8-2
	PHF11	ENST00000465045.5	TSL:1	n.54A>G		non_coding_transcript_exon	Exon 3 of 12	ENSP00000418630.1	J3KR57

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

GnomAD2 exomes AF: 0.704 AC: 176593 AN: 250890 AF XY: 0.693

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 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

African (AFR) AF: 0.882 AC: 29372 AN: 33298

American (AMR) AF: 0.767 AC: 34238 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15919 AN: 26060

East Asian (EAS) AF: 0.894 AC: 35430 AN: 39648

South Asian (SAS) AF: 0.646 AC: 55627 AN: 86070

European-Finnish (FIN) AF: 0.681 AC: 36260 AN: 53234

Middle Eastern (MID) AF: 0.636 AC: 3655 AN: 5744

European-Non Finnish (NFE) AF: 0.653 AC: 721062 AN: 1104746

Other (OTH) AF: 0.682 AC: 40978 AN: 60096

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

African (AFR) AF: 0.876 AC: 36328 AN: 41452

American (AMR) AF: 0.742 AC: 11325 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2048 AN: 3466

East Asian (EAS) AF: 0.870 AC: 4492 AN: 5164

South Asian (SAS) AF: 0.667 AC: 3213 AN: 4818

European-Finnish (FIN) AF: 0.673 AC: 7077 AN: 10518

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44143 AN: 67916

Other (OTH) AF: 0.702 AC: 1481 AN: 2110

Alfa AF: 0.680 Hom.: 145702

Bravo AF: 0.741

Asia WGS AF: 0.764 AC: 2659 AN: 3478

EpiCase AF: 0.654

EpiControl AF: 0.644

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PHF11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.88
DANN	Benign	0.55
PhyloP100		0.11
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2031532;

hg19: chr13-50080847;

COSMIC: COSV62896216;