chr16-13920198-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005236.3(ERCC4):​c.33C>T​(p.Ala11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,607,076 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 19 hom., cov: 33)
Exomes 𝑓: 0.021 ( 379 hom. )

Consequence

ERCC4
NM_005236.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.10
Variant links:
Genes affected
ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 16-13920198-C-T is Benign according to our data. Variant chr16-13920198-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 240125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-13920198-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-3.11 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0136 (2074/152360) while in subpopulation NFE AF= 0.0229 (1557/68036). AF 95% confidence interval is 0.0219. There are 19 homozygotes in gnomad4. There are 913 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ERCC4NM_005236.3 linkuse as main transcriptc.33C>T p.Ala11= synonymous_variant 1/11 ENST00000311895.8
LOC105371093XR_007065000.1 linkuse as main transcriptn.82+6327G>A intron_variant, non_coding_transcript_variant
ERCC4XM_011522424.4 linkuse as main transcriptc.33C>T p.Ala11= synonymous_variant 1/12
LOC105371093XR_007064999.1 linkuse as main transcriptn.82+6327G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERCC4ENST00000311895.8 linkuse as main transcriptc.33C>T p.Ala11= synonymous_variant 1/111 NM_005236.3 P1Q92889-1

Frequencies

GnomAD3 genomes
AF:
0.0136
AC:
2068
AN:
152242
Hom.:
19
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00562
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.00824
Gnomad ASJ
AF:
0.00778
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.00856
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0229
Gnomad OTH
AF:
0.00766
GnomAD3 exomes
AF:
0.0128
AC:
3131
AN:
243880
Hom.:
42
AF XY:
0.0125
AC XY:
1668
AN XY:
132934
show subpopulations
Gnomad AFR exome
AF:
0.00470
Gnomad AMR exome
AF:
0.00411
Gnomad ASJ exome
AF:
0.00758
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00222
Gnomad FIN exome
AF:
0.00913
Gnomad NFE exome
AF:
0.0228
Gnomad OTH exome
AF:
0.0117
GnomAD4 exome
AF:
0.0206
AC:
29950
AN:
1454716
Hom.:
379
Cov.:
35
AF XY:
0.0197
AC XY:
14266
AN XY:
724034
show subpopulations
Gnomad4 AFR exome
AF:
0.00436
Gnomad4 AMR exome
AF:
0.00445
Gnomad4 ASJ exome
AF:
0.00853
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00186
Gnomad4 FIN exome
AF:
0.0105
Gnomad4 NFE exome
AF:
0.0250
Gnomad4 OTH exome
AF:
0.0155
GnomAD4 genome
AF:
0.0136
AC:
2074
AN:
152360
Hom.:
19
Cov.:
33
AF XY:
0.0123
AC XY:
913
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.00575
Gnomad4 AMR
AF:
0.00823
Gnomad4 ASJ
AF:
0.00778
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00856
Gnomad4 NFE
AF:
0.0229
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.0199
Hom.:
28
Bravo
AF:
0.0134
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.0218
EpiControl
AF:
0.0179

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group F Benign:2
Benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 12, 2016- -
Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 11, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
4.0
DANN
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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: rs3136042; hg19: chr16-14014055; COSMIC: COSV61313691; COSMIC: COSV61313691; API