rs2535913

Positions:

• chr14-72948525-G-A

Variant summary

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

The NM_015604.4(DCAF4):​c.728+1334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,082 control chromosomes in the GnomAD database, including 5,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.27 (5914 hom., cov: 33)
• Consequence: DCAF4 NM_015604.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.40

Genes affected

DCAF4 (HGNC:20229): (DDB1 and CUL4 associated factor 4) This gene encodes a WD repeat-containing protein that interacts with the Cul4-Ddb1 E3 ligase macromolecular complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF4	NM_015604.4	c.728+1334G>A		intron_variant		ENST00000358377.7	NP_056419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF4	ENST00000358377.7	c.728+1334G>A		intron_variant		1	NM_015604.4	ENSP00000351147	A1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40808 AN: 151964 Hom.: 5911 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.236

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40826 AN: 152082 Hom.: 5914 Cov.: 33 AF XY: 0.269 AC XY: 19982 AN XY: 74336

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.238

Alfa AF: 0.281 Hom.: 1088

Bravo AF: 0.248

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Telomere length, mean leukocyte Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Aug 03, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.54

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: rs2535913; hg19: chr14-73415233;