rs4899445

Variant names:

• chr14-72807013-A-G
• rs4899445
• NM_001280542.3:c.33-35120T>C

Variant summary

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

The ENST00000556509.6(DPF3):​c.33-35120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 152,194 control chromosomes in the GnomAD database, including 758 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 0.087 (758 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: DPF3 ENST00000556509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720
• Publications: 2 publications found

Genes affected

DPF3 (HGNC:17427): (double PHD fingers 3) This gene encodes a member of the D4 protein family. The encoded protein is a transcription regulator that binds acetylated histones and is a component of the BAF chromatin remodeling complex. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556509.6. 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
	DPF3	NM_001280542.3	MANE Select	c.33-35120T>C		intron	N/A	NP_001267471.1
	DPF3	NM_001280544.2		c.198-35120T>C		intron	N/A	NP_001267473.1
	DPF3	NM_001280543.2		c.63-35120T>C		intron	N/A	NP_001267472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPF3	ENST00000556509.6	TSL:1 MANE Select	c.33-35120T>C		intron	N/A	ENSP00000450518.1
	DPF3	ENST00000381216.8	TSL:1	n.33-35120T>C		intron	N/A	ENSP00000370614.4
	DPF3	ENST00000366353.8	TSL:2	n.198-35120T>C		intron	N/A	ENSP00000381791.3

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13186 AN: 152052 Hom.: 756 Cov.: 32

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0786

GnomAD4 exome AF: 0.0833 AC: 2 AN: 24 Hom.: 0 AF XY: 0.100 AC XY: 2 AN XY: 20

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0556 AC: 1 AN: 18

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0867 AC: 13196 AN: 152170 Hom.: 758 Cov.: 32 AF XY: 0.0874 AC XY: 6506 AN XY: 74400

African (AFR) AF: 0.0617 AC: 2560 AN: 41512

American (AMR) AF: 0.183 AC: 2793 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3468

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5180

South Asian (SAS) AF: 0.191 AC: 921 AN: 4814

European-Finnish (FIN) AF: 0.0495 AC: 525 AN: 10612

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0872 AC: 5932 AN: 67996

Other (OTH) AF: 0.0773 AC: 163 AN: 2108

Alfa AF: 0.0879 Hom.: 1764

Bravo AF: 0.0922

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.73
PhyloP100		-0.72
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: rs4899445; hg19: chr14-73273721;