1-167950253-G-C

Variant names:

• chr1-167950253-G-C
• rs202274
• NM_001198956.2:c.98-1547G>C

Variant summary

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

The NM_001198956.2(DCAF6):​c.98-1547G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,978 control chromosomes in the GnomAD database, including 3,730 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 (3730 hom., cov: 33)
• Consequence: DCAF6 NM_001198956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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 (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF6	NM_001198956.2	c.98-1547G>C		intron_variant	Intron 1 of 21	ENST00000367840.4	NP_001185885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF6	ENST00000367840.4	c.98-1547G>C		intron_variant	Intron 1 of 21	1	NM_001198956.2	ENSP00000356814.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27523 AN: 151858 Hom.: 3716 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.181 AC: 27573 AN: 151978 Hom.: 3730 Cov.: 33 AF XY: 0.181 AC XY: 13469 AN XY: 74266

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.0984

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0491 Hom.: 46

Bravo AF: 0.186

Asia WGS AF: 0.0790 AC: 274 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
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: rs202274; hg19: chr1-167919491;