13-102845848-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001204425.2(BIVM-ERCC5):​c.1450+6045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 258,432 control chromosomes in the GnomAD database, including 76,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 43735 hom., cov: 34)
Exomes 𝑓: 0.78 ( 32549 hom. )

Consequence

BIVM-ERCC5
NM_001204425.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.57
Variant links:
Genes affected
ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 13-102845848-A-G is Benign according to our data. Variant chr13-102845848-A-G is described in ClinVar as [Benign]. Clinvar id is 310903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIVM-ERCC5NM_001204425.2 linkuse as main transcriptc.1450+6045A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERCC5ENST00000535557.5 linkuse as main transcriptn.8A>G non_coding_transcript_exon_variant 1/75
ERCC5ENST00000651002.1 linkuse as main transcriptc.-419A>G 5_prime_UTR_variant, NMD_transcript_variant 1/15
ERCC5ENST00000652613.1 linkuse as main transcript upstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.755
AC:
114866
AN:
152044
Hom.:
43702
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.687
Gnomad AMI
AF:
0.815
Gnomad AMR
AF:
0.682
Gnomad ASJ
AF:
0.860
Gnomad EAS
AF:
0.626
Gnomad SAS
AF:
0.714
Gnomad FIN
AF:
0.797
Gnomad MID
AF:
0.766
Gnomad NFE
AF:
0.814
Gnomad OTH
AF:
0.762
GnomAD4 exome
AF:
0.777
AC:
82596
AN:
106270
Hom.:
32549
Cov.:
0
AF XY:
0.779
AC XY:
40153
AN XY:
51518
show subpopulations
Gnomad4 AFR exome
AF:
0.681
Gnomad4 AMR exome
AF:
0.650
Gnomad4 ASJ exome
AF:
0.837
Gnomad4 EAS exome
AF:
0.644
Gnomad4 SAS exome
AF:
0.716
Gnomad4 FIN exome
AF:
0.785
Gnomad4 NFE exome
AF:
0.814
Gnomad4 OTH exome
AF:
0.788
GnomAD4 genome
AF:
0.755
AC:
114950
AN:
152162
Hom.:
43735
Cov.:
34
AF XY:
0.753
AC XY:
56042
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.687
Gnomad4 AMR
AF:
0.681
Gnomad4 ASJ
AF:
0.860
Gnomad4 EAS
AF:
0.627
Gnomad4 SAS
AF:
0.715
Gnomad4 FIN
AF:
0.797
Gnomad4 NFE
AF:
0.814
Gnomad4 OTH
AF:
0.764
Alfa
AF:
0.800
Hom.:
82408
Bravo
AF:
0.745
Asia WGS
AF:
0.700
AC:
2436
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 11, 2018This variant is associated with the following publications: (PMID: 25644244, 22982416, 22981091, 22866149, 26338418) -
Xeroderma pigmentosum, group G Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
1.2
DANN
Benign
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs751402; hg19: chr13-103498198; API