chr13-49520991-A-G

Variant names:

• chr13-49520991-A-G
• rs3765526
• NM_001040443.3:c.505+51A>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.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
• Publications: 13 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF11	NM_001040443.3	MANE Select	c.505+51A>G		intron	N/A	NP_001035533.1
	SETDB2-PHF11	NM_001320727.2		c.1987+51A>G		intron	N/A	NP_001307656.1
	PHF11	NM_001040444.3		c.388+51A>G		intron	N/A	NP_001035534.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF11	ENST00000378319.8	TSL:1 MANE Select	c.505+51A>G		intron	N/A	ENSP00000367570.3
	PHF11	ENST00000488958.5	TSL:1	c.388+51A>G		intron	N/A	ENSP00000417539.1
	PHF11	ENST00000465045.5	TSL:1	n.388+51A>G		intron	N/A	ENSP00000418630.1

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

GnomAD2 exomes AF: 0.489 AC: 105261 AN: 215366 AF XY: 0.486

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 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

African (AFR) AF: 0.274 AC: 8234 AN: 30016

American (AMR) AF: 0.517 AC: 17150 AN: 33194

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 12011 AN: 23836

East Asian (EAS) AF: 0.501 AC: 19315 AN: 38544

South Asian (SAS) AF: 0.306 AC: 22835 AN: 74646

European-Finnish (FIN) AF: 0.538 AC: 28083 AN: 52198

Middle Eastern (MID) AF: 0.495 AC: 2691 AN: 5434

European-Non Finnish (NFE) AF: 0.537 AC: 556188 AN: 1035002

Other (OTH) AF: 0.502 AC: 28159 AN: 56062

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

African (AFR) AF: 0.279 AC: 11584 AN: 41470

American (AMR) AF: 0.510 AC: 7796 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1676 AN: 3468

East Asian (EAS) AF: 0.482 AC: 2497 AN: 5180

South Asian (SAS) AF: 0.316 AC: 1526 AN: 4826

European-Finnish (FIN) AF: 0.534 AC: 5627 AN: 10540

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36703 AN: 67974

Other (OTH) AF: 0.480 AC: 1011 AN: 2108

Alfa AF: 0.496 Hom.: 3714

Bravo AF: 0.451

Asia WGS AF: 0.381 AC: 1322 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		1.1
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: rs3765526; hg19: chr13-50095127; COSMIC: COSV62896532; COSMIC: COSV62896532;