rs28720291

chr11-61322299-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.48

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]

ACMG classification

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 GnomAd at 950 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 950 AN: 152148 Hom.: 3 Cov.: 32

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.: 10 AF XY: 0.00582 AC XY: 791 AN XY: 135826

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.: 86 Cov.: 30 AF XY: 0.00828 AC XY: 6022 AN XY: 726932

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.: 3 Cov.: 32 AF XY: 0.00616 AC XY: 459 AN XY: 74462

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.: 10

Bravo AF: 0.00681

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00693

EpiControl AF: 0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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	Invitae	Oct 23, 2017	- -

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

Other links and lift over

dbSNP: rs28720291; hg19: chr11-61089771;