1-168044612-T-C

Position:

• chr1-168044612-T-C

Variant summary

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

The NM_001198956.2(DCAF6):​c.1871T>C​(p.Val624Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,609,918 control chromosomes in the GnomAD database, including 58,387 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3963 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54424 hom.)
• Consequence: DCAF6 NM_001198956.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040177405).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCAF6	NM_001198956.2	c.1871T>C	p.Val624Ala	missense_variant	15/22	ENST00000367840.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCAF6	ENST00000367840.4	c.1871T>C	p.Val624Ala	missense_variant	15/22	1	NM_001198956.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32032 AN: 151970 Hom.: 3964 Cov.: 32

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.241 AC: 60452 AN: 250876 Hom.: 7994 AF XY: 0.250 AC XY: 33920 AN XY: 135592

Gnomad AFR exome AF: 0.0786

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.275

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.268 AC: 391049 AN: 1457830 Hom.: 54424 Cov.: 31 AF XY: 0.269 AC XY: 195481 AN XY: 725392

Gnomad4 AFR exome AF: 0.0704

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.211 AC: 32028 AN: 152088 Hom.: 3963 Cov.: 32 AF XY: 0.210 AC XY: 15647 AN XY: 74348

Gnomad4 AFR AF: 0.0802

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.210

Alfa AF: 0.261 Hom.: 11636

Bravo AF: 0.191

TwinsUK AF: 0.272 AC: 1010

ALSPAC AF: 0.273 AC: 1053

ESP6500AA AF: 0.0869 AC: 383

ESP6500EA AF: 0.275 AC: 2364

ExAC AF: 0.246 AC: 29838

Asia WGS AF: 0.222 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.82
DEOGEN2	Benign	0.014	.;.;T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.57	T;T;T;T
MetaRNN	Benign	0.0040	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	.;.;L;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.24	N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.31	T;T;T;T
Sift4G	Benign	0.83	T;T;T;T
Polyphen		0.0010, 0.0050	.;B;B;B
Vest4		0.081
MPC		0.43
ClinPred		0.0057	T
GERP RS		2.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.056
gMVP		0.083

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: rs11558511; hg19: chr1-168013850; COSMIC: COSV56578818; COSMIC: COSV56578818;