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GeneBe

rs11615

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001983.4(ERCC1):c.354T>C(p.Asn118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,611,696 control chromosomes in the GnomAD database, including 163,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 26981 hom., cov: 31)
Exomes 𝑓: 0.42 ( 136082 hom. )

Consequence

ERCC1
NM_001983.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.629
Variant links:
Genes affected
ERCC1 (HGNC:3433): (ERCC excision repair 1, endonuclease non-catalytic subunit) The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 19-45420395-A-G is Benign according to our data. Variant chr19-45420395-A-G is described in ClinVar as [Benign]. Clinvar id is 225945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45420395-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.629 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ERCC1NM_001983.4 linkuse as main transcriptc.354T>C p.Asn118= synonymous_variant 4/10 ENST00000300853.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERCC1ENST00000300853.8 linkuse as main transcriptc.354T>C p.Asn118= synonymous_variant 4/101 NM_001983.4 P1P07992-1

Frequencies

GnomAD3 genomes
AF:
0.552
AC:
83875
AN:
151840
Hom.:
26919
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.875
Gnomad AMI
AF:
0.478
Gnomad AMR
AF:
0.596
Gnomad ASJ
AF:
0.396
Gnomad EAS
AF:
0.737
Gnomad SAS
AF:
0.544
Gnomad FIN
AF:
0.362
Gnomad MID
AF:
0.436
Gnomad NFE
AF:
0.373
Gnomad OTH
AF:
0.518
GnomAD3 exomes
AF:
0.501
AC:
125107
AN:
249686
Hom.:
35330
AF XY:
0.485
AC XY:
65375
AN XY:
134914
show subpopulations
Gnomad AFR exome
AF:
0.890
Gnomad AMR exome
AF:
0.705
Gnomad ASJ exome
AF:
0.415
Gnomad EAS exome
AF:
0.734
Gnomad SAS exome
AF:
0.529
Gnomad FIN exome
AF:
0.363
Gnomad NFE exome
AF:
0.374
Gnomad OTH exome
AF:
0.448
GnomAD4 exome
AF:
0.415
AC:
606069
AN:
1459736
Hom.:
136082
Cov.:
37
AF XY:
0.416
AC XY:
301953
AN XY:
726166
show subpopulations
Gnomad4 AFR exome
AF:
0.893
Gnomad4 AMR exome
AF:
0.689
Gnomad4 ASJ exome
AF:
0.405
Gnomad4 EAS exome
AF:
0.727
Gnomad4 SAS exome
AF:
0.528
Gnomad4 FIN exome
AF:
0.366
Gnomad4 NFE exome
AF:
0.370
Gnomad4 OTH exome
AF:
0.452
GnomAD4 genome
AF:
0.553
AC:
83997
AN:
151960
Hom.:
26981
Cov.:
31
AF XY:
0.554
AC XY:
41178
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.875
Gnomad4 AMR
AF:
0.596
Gnomad4 ASJ
AF:
0.396
Gnomad4 EAS
AF:
0.737
Gnomad4 SAS
AF:
0.543
Gnomad4 FIN
AF:
0.362
Gnomad4 NFE
AF:
0.373
Gnomad4 OTH
AF:
0.521
Alfa
AF:
0.414
Hom.:
34822
Bravo
AF:
0.584
Asia WGS
AF:
0.667
AC:
2322
AN:
3478
EpiCase
AF:
0.381
EpiControl
AF:
0.384

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.010
Dann
Benign
0.42
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs11615; hg19: chr19-45923653; API