13-49521817-C-G

Variant names:

• chr13-49521817-C-G
• rs2274276
• NM_001040443.3:c.506-226C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040443.3(PHF11):​c.506-226C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 301,792 control chromosomes in the GnomAD database, including 46,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20767 hom., cov: 32)
  • Exomes 𝑓: 0.57 (25427 hom.)
• Consequence: PHF11 NM_001040443.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.506-226C>G		intron_variant	Intron 5 of 9	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.506-226C>G		intron_variant	Intron 5 of 9	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77612 AN: 151850 Hom.: 20742 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.575 AC: 86083 AN: 149824 Hom.: 25427 AF XY: 0.569 AC XY: 44932 AN XY: 78910

African (AFR) AF: 0.344 AC: 1370 AN: 3982

American (AMR) AF: 0.562 AC: 2142 AN: 3814

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 2869 AN: 5096

East Asian (EAS) AF: 0.726 AC: 7193 AN: 9902

South Asian (SAS) AF: 0.441 AC: 5430 AN: 12318

European-Finnish (FIN) AF: 0.585 AC: 7755 AN: 13258

Middle Eastern (MID) AF: 0.550 AC: 383 AN: 696

European-Non Finnish (NFE) AF: 0.586 AC: 53764 AN: 91692

Other (OTH) AF: 0.571 AC: 5177 AN: 9066

GnomAD4 genome AF: 0.511 AC: 77673 AN: 151968 Hom.: 20767 Cov.: 32 AF XY: 0.511 AC XY: 37957 AN XY: 74262

African (AFR) AF: 0.351 AC: 14539 AN: 41448

American (AMR) AF: 0.561 AC: 8571 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3375 AN: 5158

South Asian (SAS) AF: 0.446 AC: 2151 AN: 4818

European-Finnish (FIN) AF: 0.577 AC: 6084 AN: 10552

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39430 AN: 67944

Other (OTH) AF: 0.519 AC: 1095 AN: 2108

Alfa AF: 0.415 Hom.: 1178

Bravo AF: 0.507

Asia WGS AF: 0.512 AC: 1774 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.76
PhyloP100		2.1
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: rs2274276; hg19: chr13-50095953;