chr13-49518350-T-C

Variant names:

• chr13-49518350-T-C
• rs7329078
• NM_001040443.3:c.458+199T>C

Variant summary

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

The NM_001320727.2(SETDB2-PHF11):​c.1940+199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 274,210 control chromosomes in the GnomAD database, including 58,378 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 0.60 (27697 hom., cov: 30)
  • Exomes 𝑓: 0.70 (30681 hom.)
• Consequence: SETDB2-PHF11 NM_001320727.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320727.2. 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.458+199T>C		intron	N/A	NP_001035533.1
	SETDB2-PHF11	NM_001320727.2		c.1940+199T>C		intron	N/A	NP_001307656.1
	PHF11	NM_001040444.3		c.341+199T>C		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.458+199T>C		intron	N/A	ENSP00000367570.3
	PHF11	ENST00000488958.5	TSL:1	c.341+199T>C		intron	N/A	ENSP00000417539.1
	PHF11	ENST00000465045.5	TSL:1	n.341+199T>C		intron	N/A	ENSP00000418630.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 90838 AN: 151114 Hom.: 27658 Cov.: 30

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.705 AC: 86646 AN: 122978 Hom.: 30681 Cov.: 2 AF XY: 0.702 AC XY: 45338 AN XY: 64586

African (AFR) AF: 0.605 AC: 2301 AN: 3804

American (AMR) AF: 0.728 AC: 3151 AN: 4328

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 3010 AN: 4546

East Asian (EAS) AF: 0.898 AC: 10896 AN: 12134

South Asian (SAS) AF: 0.615 AC: 796 AN: 1294

European-Finnish (FIN) AF: 0.728 AC: 4422 AN: 6072

Middle Eastern (MID) AF: 0.678 AC: 404 AN: 596

European-Non Finnish (NFE) AF: 0.683 AC: 56115 AN: 82156

Other (OTH) AF: 0.690 AC: 5551 AN: 8048

GnomAD4 genome AF: 0.601 AC: 90920 AN: 151232 Hom.: 27697 Cov.: 30 AF XY: 0.603 AC XY: 44565 AN XY: 73862

African (AFR) AF: 0.547 AC: 22555 AN: 41256

American (AMR) AF: 0.661 AC: 10043 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1890 AN: 3464

East Asian (EAS) AF: 0.818 AC: 4186 AN: 5120

South Asian (SAS) AF: 0.533 AC: 2563 AN: 4812

European-Finnish (FIN) AF: 0.631 AC: 6518 AN: 10332

Middle Eastern (MID) AF: 0.628 AC: 181 AN: 288

European-Non Finnish (NFE) AF: 0.610 AC: 41325 AN: 67750

Other (OTH) AF: 0.598 AC: 1258 AN: 2104

Alfa AF: 0.604 Hom.: 16700

Bravo AF: 0.605

Asia WGS AF: 0.651 AC: 2246 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.46
PhyloP100		0.18
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: rs7329078; hg19: chr13-50092486;