rs9651726

Variant names:

• chr11-61301886-T-C
• rs9651726
• NM_001923.5:c.3215+371A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 -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 rank	MANE	Protein	UniProt
DDB1	NM_001923.5	c.3215+371A>G		intron_variant	Intron 25 of 26	ENST00000301764.12	NP_001914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB1	ENST00000301764.12	c.3215+371A>G		intron_variant	Intron 25 of 26	1	NM_001923.5	ENSP00000301764.7
DDB1	ENST00000540166.5	n.3215+371A>G		intron_variant	Intron 27 of 28	2		ENSP00000440269.1

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

African (AFR) AF: 0.558 AC: 232 AN: 416

American (AMR) AF: 0.0932 AC: 180 AN: 1932

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 19 AN: 390

East Asian (EAS) AF: 0.0196 AC: 23 AN: 1174

South Asian (SAS) AF: 0.116 AC: 139 AN: 1202

European-Finnish (FIN) AF: 0.0578 AC: 23 AN: 398

Middle Eastern (MID) AF: 0.100 AC: 3 AN: 30

European-Non Finnish (NFE) AF: 0.0708 AC: 659 AN: 9302

Other (OTH) AF: 0.0883 AC: 71 AN: 804

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

African (AFR) AF: 0.631 AC: 26115 AN: 41374

American (AMR) AF: 0.155 AC: 2368 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3470

East Asian (EAS) AF: 0.0457 AC: 236 AN: 5166

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4808

European-Finnish (FIN) AF: 0.128 AC: 1351 AN: 10590

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7633 AN: 67990

Other (OTH) AF: 0.239 AC: 504 AN: 2108

Alfa AF: 0.149 Hom.: 2359

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
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs9651726; hg19: chr11-61069358;