rs9651726

chr11-61301886-T-C

Variant summary

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

The NM_001923.5(DDB1):c.3215+371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 167,640 control chromosomes in the GnomAD database, including 9,437 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 0.26 (9295 hom., cov: 31)
  • Exomes 𝑓: 0.086 (142 hom.)
• Consequence: DDB1 NM_001923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB1	NM_001923.5	c.3215+371A>G		intron_variant		ENST00000301764.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB1	ENST00000301764.12	c.3215+371A>G		intron_variant		1	NM_001923.5	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39622 AN: 151874 Hom.: 9239 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.0862 AC: 1349 AN: 15648 Hom.: 142 Cov.: 0 AF XY: 0.0846 AC XY: 699 AN XY: 8262

Gnomad4 AFR exome AF: 0.558

Gnomad4 AMR exome AF: 0.0932

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.0196

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.0578

Gnomad4 NFE exome AF: 0.0708

Gnomad4 OTH exome AF: 0.0883

GnomAD4 genome AF: 0.262 AC: 39746 AN: 151992 Hom.: 9295 Cov.: 31 AF XY: 0.259 AC XY: 19272 AN XY: 74294

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.0457

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.239

Alfa AF: 0.148 Hom.: 1713

Bravo AF: 0.279

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.4
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

Other links and lift over

dbSNP: rs9651726; hg19: chr11-61069358;