13-49496108-GGGGCGGGCGGGCGGGC-GGGGCGGGC

Variant names:

• chr13-49496108-GGGGCGGGC-G
• rs370049093
• NM_001040443.3:c.94+29_94+36delCGGGCGGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001040443.3(PHF11):​c.94+29_94+36delCGGGCGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 690,630 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: PHF11 NM_001040443.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.94+29_94+36delCGGGCGGG		intron_variant	Intron 1 of 9	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.94+14_94+21delGGGCGGGC		intron_variant	Intron 1 of 9	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes AF: 0.000153 AC: 23 AN: 149916 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000295

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000252

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.00 AC: 0 AN: 94 AF XY: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000202 AC: 109 AN: 540604 Hom.: 0 AF XY: 0.000187 AC XY: 50 AN XY: 267532

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11676

American (AMR) AF: 0.000144 AC: 1 AN: 6962

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 3 AN: 10400

East Asian (EAS) AF: 0.000185 AC: 4 AN: 21666

South Asian (SAS) AF: 0.000359 AC: 8 AN: 22310

European-Finnish (FIN) AF: 0.00107 AC: 25 AN: 23448

Middle Eastern (MID) AF: 0.000565 AC: 1 AN: 1770

European-Non Finnish (NFE) AF: 0.000149 AC: 62 AN: 417086

Other (OTH) AF: 0.000198 AC: 5 AN: 25286

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000153 AC: 23 AN: 150026 Hom.: 0 Cov.: 0 AF XY: 0.000123 AC XY: 9 AN XY: 73182

African (AFR) AF: 0.0000488 AC: 2 AN: 40958

American (AMR) AF: 0.00 AC: 0 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 4910

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.000295 AC: 3 AN: 10154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000253 AC: 17 AN: 67322

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00129 Hom.: 1272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370049093; hg19: chr13-50070244;