rs1060041

Variant names:

• chr1-168004738-C-T
• rs1060041
• NM_001198956.2:c.1323C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001198956.2(DCAF6):​c.1323C>T​(p.Asp441Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,613,710 control chromosomes in the GnomAD database, including 48,898 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 0.20 (3842 hom., cov: 32)
  • Exomes 𝑓: 0.24 (45056 hom.)
• Consequence: DCAF6 NM_001198956.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 19 publications found

Genes affected

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.217 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198956.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF6	NM_001198956.2	MANE Select	c.1323C>T	p.Asp441Asp	synonymous	Exon 10 of 22	NP_001185885.1	Q58WW2-3
	DCAF6	NM_001349773.2		c.1323C>T	p.Asp441Asp	synonymous	Exon 10 of 21	NP_001336702.1
	DCAF6	NM_001198957.2		c.1230C>T	p.Asp410Asp	synonymous	Exon 9 of 21	NP_001185886.1	Q58WW2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF6	ENST00000367840.4	TSL:1 MANE Select	c.1323C>T	p.Asp441Asp	synonymous	Exon 10 of 22	ENSP00000356814.3	Q58WW2-3
	DCAF6	ENST00000312263.10	TSL:1	c.1323C>T	p.Asp441Asp	synonymous	Exon 10 of 19	ENSP00000311949.6	Q58WW2-1
	DCAF6	ENST00000856062.1		c.1323C>T	p.Asp441Asp	synonymous	Exon 10 of 22	ENSP00000526121.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30879 AN: 151998 Hom.: 3839 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.219

GnomAD2 exomes AF: 0.246 AC: 61155 AN: 248920 AF XY: 0.239

Gnomad AFR exome AF: 0.0763

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.241 AC: 352071 AN: 1461594 Hom.: 45056 Cov.: 35 AF XY: 0.239 AC XY: 174121 AN XY: 727106

African (AFR) AF: 0.0739 AC: 2474 AN: 33474

American (AMR) AF: 0.470 AC: 21016 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 6402 AN: 26118

East Asian (EAS) AF: 0.137 AC: 5444 AN: 39692

South Asian (SAS) AF: 0.192 AC: 16590 AN: 86244

European-Finnish (FIN) AF: 0.204 AC: 10873 AN: 53408

Middle Eastern (MID) AF: 0.250 AC: 1440 AN: 5768

European-Non Finnish (NFE) AF: 0.247 AC: 274300 AN: 1111792

Other (OTH) AF: 0.224 AC: 13532 AN: 60390

GnomAD4 genome AF: 0.203 AC: 30891 AN: 152116 Hom.: 3842 Cov.: 32 AF XY: 0.205 AC XY: 15214 AN XY: 74358

African (AFR) AF: 0.0809 AC: 3360 AN: 41524

American (AMR) AF: 0.364 AC: 5550 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3466

East Asian (EAS) AF: 0.137 AC: 709 AN: 5176

South Asian (SAS) AF: 0.189 AC: 914 AN: 4824

European-Finnish (FIN) AF: 0.209 AC: 2211 AN: 10580

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16475 AN: 67970

Other (OTH) AF: 0.219 AC: 463 AN: 2112

Alfa AF: 0.225 Hom.: 2674

Bravo AF: 0.213

Asia WGS AF: 0.160 AC: 557 AN: 3478

EpiCase AF: 0.243

EpiControl AF: 0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.7
DANN	Benign	0.44
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1060041; hg19: chr1-167973976; COSMIC: COSV56582776;