Variant rs28720291 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001923.5(DDB1):c.1119G>A(p.Gly373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00828 in 1,613,476 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 86 hom. )

Consequence

DDB1
NM_001923.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.48

Variant links:

Genes affected

DDB1 (HGNC:2717): (damage specific DNA binding protein 1) The protein encoded by this gene is the large subunit (p127) of the heterodimeric DNA damage-binding (DDB) complex while another protein (p48) forms the small subunit. This protein complex functions in nucleotide-excision repair and binds to DNA following UV damage. Defective activity of this complex causes the repair defect in patients with xeroderma pigmentosum complementation group E (XPE) - an autosomal recessive disorder characterized by photosensitivity and early onset of carcinomas. However, it remains for mutation analysis to demonstrate whether the defect in XPE patients is in this gene or the gene encoding the small subunit. In addition, Best vitelliform mascular dystrophy is mapped to the same region as this gene on 11q, but no sequence alternations of this gene are demonstrated in Best disease patients. The protein encoded by this gene also functions as an adaptor molecule for the cullin 4 (CUL4) ubiquitin E3 ligase complex by facilitating the binding of substrates to this complex and the ubiquitination of proteins. [provided by RefSeq, May 2012]

DDB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 11-61322299-C-T is Benign according to our data. Variant chr11-61322299-C-T is described in ClinVar as [Benign]. Clinvar id is 782214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.47 with no splicing effect.

BS2

High AC in GnomAd4 at 951 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDB1	NM_001923.5 linkuse as main transcript	c.1119G>A	p.Gly373=	synonymous_variant	9/27	ENST00000301764.12	NP_001914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB1	ENST00000301764.12 linkuse as main transcript	c.1119G>A	p.Gly373=	synonymous_variant	9/27	1	NM_001923.5	ENSP00000301764	P1	Q16531-1

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

950

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00590

AC:

1484

AN:

251318

Hom.:

AF XY:

0.00582

AC XY:

791

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00849

AC:

12412

AN:

1461210

Hom.:

Cov.:

AF XY:

0.00828

AC XY:

6022

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00393

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.00625

AC:

951

AN:

152266

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

459

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00839

Hom.:

Bravo

AF:

0.00681

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00693

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	DDB1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 23, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.7

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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