14-72926538-G-C

Variant names:

• chr14-72926538-G-C
• rs3213729
• NM_015604.4:c.-14G>C

Variant summary

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

The NM_015604.4(DCAF4):​c.-14G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,378 control chromosomes in the GnomAD database, including 4,744 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 0.18 (4744 hom., cov: 33)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: DCAF4 NM_015604.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF4	NM_015604.4	c.-14G>C		5_prime_UTR_variant	Exon 1 of 14	ENST00000358377.7	NP_056419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF4	ENST00000358377.7	c.-14G>C		5_prime_UTR_variant	Exon 1 of 14	1	NM_015604.4	ENSP00000351147.2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26701 AN: 152126 Hom.: 4731 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.0373 AC: 5 AN: 134 Hom.: 0 Cov.: 0 AF XY: 0.0510 AC XY: 5 AN XY: 98

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) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0357 AC: 4 AN: 112

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.176 AC: 26747 AN: 152244 Hom.: 4744 Cov.: 33 AF XY: 0.169 AC XY: 12545 AN XY: 74440

African (AFR) AF: 0.457 AC: 18980 AN: 41514

American (AMR) AF: 0.0950 AC: 1454 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 207 AN: 3472

East Asian (EAS) AF: 0.186 AC: 966 AN: 5182

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4824

European-Finnish (FIN) AF: 0.0184 AC: 195 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0643 AC: 4376 AN: 68010

Other (OTH) AF: 0.155 AC: 326 AN: 2110

Alfa AF: 0.0151 Hom.: 12

Bravo AF: 0.197

Asia WGS AF: 0.114 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		-1.4
PromoterAI		-0.043	Neutral
Mutation Taster		=298/2	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: rs3213729; hg19: chr14-73393246;