13-49513006-T-C

Variant names:

• chr13-49513006-T-C
• rs2247119
• NM_001040443.3:c.217-53T>C

Variant summary

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

The NM_001040443.3(PHF11):​c.217-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 851,258 control chromosomes in the GnomAD database, including 34,490 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 0.24 (5030 hom., cov: 32)
  • Exomes 𝑓: 0.28 (29460 hom.)
• Consequence: PHF11 NM_001040443.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 17 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.217-53T>C		intron_variant	Intron 2 of 9	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.217-53T>C		intron_variant	Intron 2 of 9	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36352 AN: 152020 Hom.: 5029 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.284 AC: 198735 AN: 699120 Hom.: 29460 AF XY: 0.281 AC XY: 104529 AN XY: 371988

African (AFR) AF: 0.0942 AC: 1548 AN: 16440

American (AMR) AF: 0.335 AC: 10234 AN: 30536

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 5593 AN: 18590

East Asian (EAS) AF: 0.371 AC: 12262 AN: 33018

South Asian (SAS) AF: 0.187 AC: 11357 AN: 60702

European-Finnish (FIN) AF: 0.237 AC: 12004 AN: 50732

Middle Eastern (MID) AF: 0.322 AC: 1328 AN: 4120

European-Non Finnish (NFE) AF: 0.299 AC: 134586 AN: 450414

Other (OTH) AF: 0.284 AC: 9823 AN: 34568

GnomAD4 genome AF: 0.239 AC: 36348 AN: 152138 Hom.: 5030 Cov.: 32 AF XY: 0.238 AC XY: 17696 AN XY: 74390

African (AFR) AF: 0.0978 AC: 4063 AN: 41528

American (AMR) AF: 0.319 AC: 4882 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3468

East Asian (EAS) AF: 0.375 AC: 1938 AN: 5162

South Asian (SAS) AF: 0.187 AC: 901 AN: 4826

European-Finnish (FIN) AF: 0.231 AC: 2440 AN: 10582

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20251 AN: 67974

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.281 Hom.: 7008

Bravo AF: 0.247

Asia WGS AF: 0.259 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.036
DANN	Benign	0.57
PhyloP100		-1.4
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: rs2247119; hg19: chr13-50087142; COSMIC: COSV62896672;