5-60940379-A-G

Variant summary

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

The NM_000082.4(ERCC8):c.77+4553T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,190 control chromosomes in the GnomAD database, including 58,350 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 0.87 (58350 hom., cov: 32)
• Consequence: ERCC8 NM_000082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC8	NM_000082.4	c.77+4553T>C		intron_variant		ENST00000676185.1
ERCC8	NM_001007233.3	c.-316+4553T>C		intron_variant
ERCC8	NM_001007234.3	c.77+4553T>C		intron_variant
ERCC8	NM_001290285.2	c.-301+4553T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC8	ENST00000676185.1	c.77+4553T>C		intron_variant			NM_000082.4	P1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132854 AN: 152072 Hom.: 58320 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.874 AC: 132938 AN: 152190 Hom.: 58350 Cov.: 32 AF XY: 0.874 AC XY: 65050 AN XY: 74396

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.870

Alfa AF: 0.885 Hom.: 7416

Bravo AF: 0.868

Asia WGS AF: 0.913 AC: 3176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs158937; hg19: chr5-60236206;