Variant rs4253231 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000124.4(ERCC6):c.*53T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,557,202 control chromosomes in the GnomAD database, including 9,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 888 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8535 hom. )

Consequence

ERCC6
NM_000124.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.478

Variant links:

Genes affected

ERCC6 (HGNC:3438): (ERCC excision repair 6, chromatin remodeling factor) This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene. [provided by RefSeq, Mar 2016]

ERCC6 links:

(HGNC:):

links:

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 10-49458762-A-G is Benign according to our data. Variant chr10-49458762-A-G is described in ClinVar as [Benign]. Clinvar id is 300031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC6	NM_000124.4 linkuse as main transcript	c.*53T>C		3_prime_UTR_variant	21/21	ENST00000355832.10	NP_000115.1
ERCC6	NM_001346440.2 linkuse as main transcript	c.*53T>C		3_prime_UTR_variant	21/21		NP_001333369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC6	ENST00000355832.10 linkuse as main transcript	c.*53T>C		3_prime_UTR_variant	21/21	1	NM_000124.4	ENSP00000348089	P1	Q03468-1
	ENST00000423283.1 linkuse as main transcript	n.235-13941A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15609

AN:

152140

Hom.:

882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.0701

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0855

Gnomad OTH

AF:

0.0914

GnomAD4 exome

AF:

0.103

AC:

144284

AN:

1404944

Hom.:

8535

Cov.:

AF XY:

0.104

AC XY:

73369

AN XY:

702242

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.0838

Gnomad4 EAS exome

AF:

0.186

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.0743

Gnomad4 NFE exome

AF:

0.0912

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.103

AC:

15637

AN:

152258

Hom.:

888

Cov.:

AF XY:

0.105

AC XY:

7819

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.0740

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.0701

Gnomad4 NFE

AF:

0.0856

Gnomad4 OTH

AF:

0.0975

Alfa

AF:

0.0921

Hom.:

1203

Bravo

AF:

0.108

Asia WGS

AF:

0.192

AC:

666

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

COFS syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cockayne syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Macular degeneration

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.8

DANN

Benign

0.84

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over