Variant rs201126529 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_000082.4(ERCC8):c.482-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 1,610,122 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

ERCC8
NM_000082.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

ERCC8 (HGNC:3439): (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

ERCC8 links:

ERCC8 (HGNC:):

ERCC8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 5-60903733-G-A is Benign according to our data. Variant chr5-60903733-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 254943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000395 (60/151918) while in subpopulation EAS AF= 0.00387 (20/5172). AF 95% confidence interval is 0.00256. There are 1 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ERCC8	NM_000082.4 linkuse as main transcript	c.482-17C>T	intron_variant	ENST00000676185.1	NP_000073.1	Q13216-1
ERCC8	NM_001007233.3 linkuse as main transcript	c.308-17C>T	intron_variant		NP_001007234.1	B3KPW7
ERCC8	NM_001290285.2 linkuse as main transcript	c.23-17C>T	intron_variant		NP_001277214.1	B3KPW7B4DGZ9
ERCC8	NM_001007234.3 linkuse as main transcript	c.482-17C>T	intron_variant		NP_001007235.1	Q13216-2A0A0S2Z3L1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC8	ENST00000676185.1 linkuse as main transcript	c.482-17C>T		intron_variant			NM_000082.4	ENSP00000501614.1		Q13216-1

Frequencies

GnomAD3 genomes

AF:

0.000395

AC:

AN:

151800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000551

AC:

138

AN:

250412

Hom.:

AF XY:

0.000539

AC XY:

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00418

Gnomad EAS exome

AF:

0.00223

Gnomad SAS exome

AF:

0.000329

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000368

AC:

537

AN:

1458204

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

261

AN XY:

725532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00468

Gnomad4 EAS exome

AF:

0.00521

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.0000865

Gnomad4 OTH exome

AF:

0.000482

GnomAD4 genome

AF:

0.000395

AC:

AN:

151918

Hom.:

Cov.:

AF XY:

0.000539

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00142

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000502

Hom.:

Bravo

AF:

0.000268

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.54

DANN

Benign

0.55

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