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GeneBe

rs17655

Variant summary

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

The NM_000123.4(ERCC5):c.3310G>C(p.Asp1104His) variant causes a missense change. The variant allele was found at a frequency of 0.243 in 1,613,874 control chromosomes in the GnomAD database, including 52,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7842 hom., cov: 32)
Exomes 𝑓: 0.24 ( 44770 hom. )

Consequence

ERCC5
NM_000123.4 missense

Scores

1
1
9

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 5.18
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 (MetaRNN=2.9867887E-4).
BP6
Variant 13-102875652-G-C is Benign according to our data. Variant chr13-102875652-G-C is described in ClinVar as [Benign]. Clinvar id is 129011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102875652-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ERCC5NM_000123.4 linkuse as main transcriptc.3310G>C p.Asp1104His missense_variant 15/15 ENST00000652225.2
BIVM-ERCC5NM_001204425.2 linkuse as main transcriptc.4672G>C p.Asp1558His missense_variant 23/23

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERCC5ENST00000652225.2 linkuse as main transcriptc.3310G>C p.Asp1104His missense_variant 15/15 NM_000123.4 P1P28715-1

Frequencies

GnomAD3 genomes
AF:
0.303
AC:
45995
AN:
151936
Hom.:
7831
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.453
Gnomad AMI
AF:
0.181
Gnomad AMR
AF:
0.292
Gnomad ASJ
AF:
0.274
Gnomad EAS
AF:
0.492
Gnomad SAS
AF:
0.243
Gnomad FIN
AF:
0.240
Gnomad MID
AF:
0.335
Gnomad NFE
AF:
0.217
Gnomad OTH
AF:
0.305
GnomAD3 exomes
AF:
0.278
AC:
69697
AN:
251078
Hom.:
10863
AF XY:
0.267
AC XY:
36243
AN XY:
135674
show subpopulations
Gnomad AFR exome
AF:
0.463
Gnomad AMR exome
AF:
0.330
Gnomad ASJ exome
AF:
0.277
Gnomad EAS exome
AF:
0.494
Gnomad SAS exome
AF:
0.227
Gnomad FIN exome
AF:
0.239
Gnomad NFE exome
AF:
0.221
Gnomad OTH exome
AF:
0.271
GnomAD4 exome
AF:
0.237
AC:
346299
AN:
1461818
Hom.:
44770
Cov.:
43
AF XY:
0.235
AC XY:
171187
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.464
Gnomad4 AMR exome
AF:
0.325
Gnomad4 ASJ exome
AF:
0.282
Gnomad4 EAS exome
AF:
0.529
Gnomad4 SAS exome
AF:
0.228
Gnomad4 FIN exome
AF:
0.243
Gnomad4 NFE exome
AF:
0.214
Gnomad4 OTH exome
AF:
0.261
GnomAD4 genome
AF:
0.303
AC:
46051
AN:
152056
Hom.:
7842
Cov.:
32
AF XY:
0.303
AC XY:
22496
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.453
Gnomad4 AMR
AF:
0.292
Gnomad4 ASJ
AF:
0.274
Gnomad4 EAS
AF:
0.492
Gnomad4 SAS
AF:
0.243
Gnomad4 FIN
AF:
0.240
Gnomad4 NFE
AF:
0.217
Gnomad4 OTH
AF:
0.305
Alfa
AF:
0.244
Hom.:
3790
Bravo
AF:
0.320
TwinsUK
AF:
0.207
AC:
766
ALSPAC
AF:
0.210
AC:
809
ESP6500AA
AF:
0.456
AC:
2009
ESP6500EA
AF:
0.229
AC:
1968
ExAC
AF:
0.277
AC:
33673
Asia WGS
AF:
0.388
AC:
1348
AN:
3478
EpiCase
AF:
0.222
EpiControl
AF:
0.230

ClinVar

Significance: Benign
Submissions summary: Benign:8Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group G Benign:3
Benign, criteria provided, single submitterclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical CenterSep 21, 2015- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 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. -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
not specified Benign:2Other:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided, no classification providedreference populationITMISep 19, 2013- -
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018This variant is associated with the following publications: (PMID: 16738949, 21390047, 24728327, 22815677, 14729591, 27153395, 24802942) -
Cerebrooculofacioskeletal syndrome 3 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.54
Cadd
Benign
22
Dann
Uncertain
0.99
Eigen
Benign
0.16
Eigen_PC
Benign
0.026
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.32
T;T;.;T;T
MetaRNN
Benign
0.00030
T;T;T;T;T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
0.0037
P;P
Polyphen
0.99
.;.;.;D;.
Vest4
0.29, 0.25
MPC
0.52
ClinPred
0.017
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.26

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.

Other links and lift over

dbSNP: rs17655; hg19: chr13-103528002; COSMIC: COSV63243750; COSMIC: COSV63243750; API