chr13-49520991-A-G

Position:

• chr13-49520991-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040443.3(PHF11):​c.505+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,500,974 control chromosomes in the GnomAD database, including 199,620 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 0.45 (16699 hom., cov: 33)
  • Exomes 𝑓: 0.51 (182921 hom.)
• Consequence: PHF11 NM_001040443.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF11	NM_001040443.3	c.505+51A>G		intron_variant		ENST00000378319.8
SETDB2-PHF11	NR_135324.2	n.2951+51A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF11	ENST00000378319.8	c.505+51A>G		intron_variant		1	NM_001040443.3	P2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68953 AN: 151924 Hom.: 16689 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.482

GnomAD3 exomes AF: 0.489 AC: 105261 AN: 215366 Hom.: 26676 AF XY: 0.486 AC XY: 57014 AN XY: 117420

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.527

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.492

Gnomad SAS exome AF: 0.308

Gnomad FIN exome AF: 0.543

Gnomad NFE exome AF: 0.539

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.515 AC: 694666 AN: 1348932 Hom.: 182921 Cov.: 21 AF XY: 0.511 AC XY: 343151 AN XY: 671642

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.454 AC: 68981 AN: 152042 Hom.: 16699 Cov.: 33 AF XY: 0.452 AC XY: 33566 AN XY: 74308

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.480

Alfa AF: 0.501 Hom.: 3675

Bravo AF: 0.451

Asia WGS AF: 0.381 AC: 1322 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.74

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: rs3765526; hg19: chr13-50095127; COSMIC: COSV62896532; COSMIC: COSV62896532;