Variant chr10-49539034-G-T 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.-87C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 152,628 control chromosomes in the GnomAD database, including 676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 676 hom., cov: 34)

Exomes 𝑓: 0.057 ( 0 hom. )

Consequence

ERCC6
NM_000124.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.199

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:

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=-0.82).

BP6

Variant 10-49539034-G-T is Benign according to our data. Variant chr10-49539034-G-T is described in ClinVar as [Benign]. Clinvar id is 300101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-49539034-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
ERCC6	NM_000124.4 link	c.-87C>A	5_prime_UTR_variant	1/21	ENST00000355832.10	NP_000115.1	Q03468-1Q59FF6
ERCC6	NM_001277058.2 link	c.-87C>A	5_prime_UTR_variant	1/6	ENST00000447839.7	NP_001263987.1	P0DP91-1A8K4Q3
ERCC6	NM_001346440.2 link	c.-83C>A	5_prime_UTR_variant	1/21		NP_001333369.1	Q03468-1
ERCC6	NM_001277059.2 link	c.-15+398C>A	intron_variant			NP_001263988.1	P0DP91-1A8K4Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC6	ENST00000355832.10 link	c.-87C>A		5_prime_UTR_variant	1/21	1	NM_000124.4	ENSP00000348089.5		Q03468-1
ERCC6	ENST00000447839.7 link	c.-87C>A		5_prime_UTR_variant	1/6	2	NM_001277058.2	ENSP00000387966.2		P0DP91-1

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8357

AN:

152214

Hom.:

677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.0805

Gnomad FIN

AF:

0.0868

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0554

GnomAD4 exome

AF:

0.0574

AC:

AN:

296

Hom.:

Cov.:

AF XY:

0.0522

AC XY:

AN XY:

230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0430

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.0549

AC:

8361

AN:

152332

Hom.:

676

Cov.:

AF XY:

0.0607

AC XY:

4525

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.364

Gnomad4 SAS

AF:

0.0808

Gnomad4 FIN

AF:

0.0868

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0577

Alfa

AF:

0.0176

Hom.:

Bravo

AF:

0.0600

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	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.82

CADD

Benign

3.3

DANN

Benign

0.66

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