rs4647707

Variant names:

• chr11-47215017-G-A
• rs4647707
• NM_000107.3:c.-120G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-47215017-G-A
• chr11-47215017-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000107.3(DDB2):​c.-120G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,493,168 control chromosomes in the GnomAD database, including 4,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (2133 hom., cov: 31)
  • Exomes 𝑓: 0.0097 (1887 hom.)
• Consequence: DDB2 NM_000107.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.284
• Publications: 7 publications found

Genes affected

DDB2 (HGNC:2718): (damage specific DNA binding protein 2) This gene encodes a protein that is necessary for the repair of ultraviolet light-damaged DNA. This protein is the smaller subunit of a heterodimeric protein complex that participates in nucleotide excision repair, and this complex mediates the ubiquitylation of histones H3 and H4, which facilitates the cellular response to DNA damage. This subunit appears to be required for DNA binding. Mutations in this gene cause xeroderma pigmentosum complementation group E, a recessive disease that is characterized by an increased sensitivity to UV light and a high predisposition for skin cancer development, in some cases accompanied by neurological abnormalities. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

DDB2 Gene-Disease associations (from GenCC):

• xeroderma pigmentosum group E

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 11-47215017-G-A is Benign according to our data. Variant chr11-47215017-G-A is described in ClinVar as Benign. ClinVar VariationId is 304913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000107.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	NM_000107.3	MANE Select	c.-120G>A		5_prime_UTR	Exon 1 of 10	NP_000098.1	Q92466-1
	DDB2	NM_001399878.1		c.-120G>A		5_prime_UTR	Exon 1 of 9	NP_001386807.1	Q92466-4
	DDB2	NM_001300734.2		c.-120G>A		5_prime_UTR	Exon 1 of 6	NP_001287663.1	Q92466-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000256996.9	TSL:1 MANE Select	c.-120G>A		5_prime_UTR	Exon 1 of 10	ENSP00000256996.4	Q92466-1
	DDB2	ENST00000915751.1		c.-120G>A		5_prime_UTR	Exon 1 of 10	ENSP00000585810.1
	DDB2	ENST00000896515.1		c.-120G>A		5_prime_UTR	Exon 1 of 10	ENSP00000566574.1

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13978 AN: 152014 Hom.: 2132 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0697

GnomAD4 exome AF: 0.00974 AC: 13060 AN: 1341036 Hom.: 1887 Cov.: 20 AF XY: 0.00842 AC XY: 5664 AN XY: 673040

African (AFR) AF: 0.333 AC: 10299 AN: 30898

American (AMR) AF: 0.0165 AC: 730 AN: 44178

Ashkenazi Jewish (ASJ) AF: 0.00365 AC: 92 AN: 25216

East Asian (EAS) AF: 0.00 AC: 0 AN: 38962

South Asian (SAS) AF: 0.00119 AC: 99 AN: 83262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48382

Middle Eastern (MID) AF: 0.0208 AC: 115 AN: 5520

European-Non Finnish (NFE) AF: 0.000542 AC: 547 AN: 1008336

Other (OTH) AF: 0.0209 AC: 1178 AN: 56282

GnomAD4 genome AF: 0.0920 AC: 13997 AN: 152132 Hom.: 2133 Cov.: 31 AF XY: 0.0891 AC XY: 6625 AN XY: 74388

African (AFR) AF: 0.320 AC: 13259 AN: 41452

American (AMR) AF: 0.0310 AC: 473 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68006

Other (OTH) AF: 0.0690 AC: 146 AN: 2116

Alfa AF: 0.0304 Hom.: 301

Bravo AF: 0.104

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Xeroderma pigmentosum, group E (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.28
PromoterAI		-0.13	Neutral
Mutation Taster		=300/0	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: rs4647707; hg19: chr11-47236568;