1-168044612-T-C

Variant names:

• chr1-168044612-T-C
• rs11558511
• NM_001198956.2:c.1871T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 35 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 -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 rank	MANE	Protein	UniProt
DCAF6	NM_001198956.2	c.1871T>C	p.Val624Ala	missense_variant	Exon 15 of 22	ENST00000367840.4	NP_001185885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF6	ENST00000367840.4	c.1871T>C	p.Val624Ala	missense_variant	Exon 15 of 22	1	NM_001198956.2	ENSP00000356814.3

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

GnomAD2 exomes AF: 0.241 AC: 60452 AN: 250876 AF XY: 0.250

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 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

African (AFR) AF: 0.0704 AC: 2355 AN: 33432

American (AMR) AF: 0.117 AC: 5220 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 7645 AN: 26070

East Asian (EAS) AF: 0.224 AC: 8877 AN: 39630

South Asian (SAS) AF: 0.273 AC: 23486 AN: 86148

European-Finnish (FIN) AF: 0.315 AC: 16827 AN: 53390

Middle Eastern (MID) AF: 0.225 AC: 1288 AN: 5724

European-Non Finnish (NFE) AF: 0.279 AC: 309675 AN: 1108496

Other (OTH) AF: 0.260 AC: 15676 AN: 60254

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

African (AFR) AF: 0.0802 AC: 3330 AN: 41514

American (AMR) AF: 0.149 AC: 2281 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3468

East Asian (EAS) AF: 0.211 AC: 1092 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1280 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3183 AN: 10570

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19115 AN: 67950

Other (OTH) AF: 0.210 AC: 441 AN: 2104

Alfa AF: 0.256 Hom.: 21803

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;.
PhyloP100		0.067
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
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs11558511; hg19: chr1-168013850; COSMIC: COSV56578818; COSMIC: COSV56578818;