dbSNP rs9651726: DDB1:c.3215+371A>G (chr11-61301886-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.548

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 -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 link	c.3215+371A>G		intron_variant	Intron 25 of 26	ENST00000301764.12	NP_001914.3	Q16531-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB1	ENST00000301764.12 link	c.3215+371A>G		intron_variant	Intron 25 of 26	1	NM_001923.5	ENSP00000301764.7		Q16531-1
DDB1	ENST00000540166.5 link	n.3215+371A>G		intron_variant	Intron 27 of 28	2		ENSP00000440269.1		F5GY55

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39622

AN:

151874

Hom.:

9239

Cov.:

show subpopulations

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.:

AF XY:

0.0846

AC XY:

699

AN XY:

8262

show subpopulations

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.:

AF XY:

0.259

AC XY:

19272

AN XY:

74294

show subpopulations

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over