rs158938

chr5-60939413-G-Achr5-60939413-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000082.4(ERCC8):c.77+5519C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,958 control chromosomes in the GnomAD database, including 33,538 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33538 hom., cov: 31)
• Consequence: ERCC8 NM_000082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC8	NM_000082.4	c.77+5519C>T		intron_variant		ENST00000676185.1
ERCC8	NM_001007233.3	c.-316+5519C>T		intron_variant
ERCC8	NM_001007234.3	c.77+5519C>T		intron_variant
ERCC8	NM_001290285.2	c.-301+5519C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC8	ENST00000676185.1	c.77+5519C>T		intron_variant			NM_000082.4	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100327 AN: 151840 Hom.: 33515 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.661 AC: 100391 AN: 151958 Hom.: 33538 Cov.: 31 AF XY: 0.663 AC XY: 49252 AN XY: 74266

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.655

Alfa AF: 0.635 Hom.: 3653

Bravo AF: 0.664

Asia WGS AF: 0.829 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.7
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs158938; hg19: chr5-60235240;