Variant chr1-160238649-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_015726.4(DCAF8):c.822G>A(p.Lys274Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,613,470 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 62 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 80 hom. )

Consequence

DCAF8
NM_015726.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

DCAF8 (HGNC:24891): (DDB1 and CUL4 associated factor 8) 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]

DCAF8 links:

DCAF8 (HGNC:):

DCAF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.21).

BP6

Variant 1-160238649-C-T is Benign according to our data. Variant chr1-160238649-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.69 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0159 (2415/152330) while in subpopulation AFR AF= 0.0487 (2023/41580). AF 95% confidence interval is 0.0469. There are 62 homozygotes in gnomad4. There are 1161 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2415 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF8	NM_015726.4 linkuse as main transcript	c.822G>A	p.Lys274Lys	synonymous_variant	5/14	ENST00000368074.6	NP_056541.2	Q5TAQ9-1B7Z8C9
DCAF8	NR_028103.2 linkuse as main transcript	n.1355G>A		non_coding_transcript_exon_variant	5/14
DCAF8	NR_028104.2 linkuse as main transcript	n.1281G>A		non_coding_transcript_exon_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF8	ENST00000368074.6 linkuse as main transcript	c.822G>A	p.Lys274Lys	synonymous_variant	5/14	5	NM_015726.4	ENSP00000357053.1		Q5TAQ9-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2418

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00833

AC:

2085

AN:

250360

Hom.:

AF XY:

0.00630

AC XY:

853

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.0505

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0221

Gnomad SAS exome

AF:

0.000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00315

AC:

4605

AN:

1461140

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

2032

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.0467

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0397

Gnomad4 SAS exome

AF:

0.000662

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.00474

GnomAD4 genome

AF:

0.0159

AC:

2415

AN:

152330

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1161

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0487

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0280

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00678

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Giant axonal neuropathy 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 14, 2022

- -

DCAF8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over