rs28720291

Variant names:

• chr11-61322299-C-T
• rs28720291
• NM_001923.5:c.1119G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001923.5(DDB1):​c.1119G>A​(p.Gly373Gly) 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:3
• Conservation: PhyloP100: -2.48
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• White-Kernohan syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001923.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB1	NM_001923.5	MANE Select	c.1119G>A	p.Gly373Gly	synonymous	Exon 9 of 27	NP_001914.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB1	ENST00000301764.12	TSL:1 MANE Select	c.1119G>A	p.Gly373Gly	synonymous	Exon 9 of 27	ENSP00000301764.7
	DDB1	ENST00000540166.5	TSL:2	n.1119G>A		non_coding_transcript_exon	Exon 11 of 29	ENSP00000440269.1
	DDB1	ENST00000954153.1		c.1119G>A	p.Gly373Gly	synonymous	Exon 9 of 28	ENSP00000624212.1

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

GnomAD2 exomes AF: 0.00590 AC: 1484 AN: 251318 AF XY: 0.00582

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 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

African (AFR) AF: 0.00126 AC: 42 AN: 33462

American (AMR) AF: 0.00333 AC: 149 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26124

East Asian (EAS) AF: 0.000680 AC: 27 AN: 39698

South Asian (SAS) AF: 0.00116 AC: 100 AN: 86246

European-Finnish (FIN) AF: 0.00393 AC: 210 AN: 53420

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0103 AC: 11397 AN: 1111386

Other (OTH) AF: 0.00795 AC: 480 AN: 60382

GnomAD4 genome AF: 0.00625 AC: 951 AN: 152266 Hom.: 3 Cov.: 32 AF XY: 0.00616 AC XY: 459 AN XY: 74462

African (AFR) AF: 0.00245 AC: 102 AN: 41548

American (AMR) AF: 0.00497 AC: 76 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 682 AN: 68026

Other (OTH) AF: 0.00522 AC: 11 AN: 2108

Alfa AF: 0.00837 Hom.: 13

Bravo AF: 0.00681

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00693

EpiControl AF: 0.0103

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs28720291; hg19: chr11-61089771;