rs4647128

chr5-60887717-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000082.4(ERCC8):c.1042-197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 152,320 control chromosomes in the GnomAD database, including 62 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 0.024 (62 hom., cov: 33)
• Consequence: ERCC8 NM_000082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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=-0.64).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.024 (3658/152320) while in subpopulation NFE AF= 0.0374 (2541/68006). AF 95% confidence interval is 0.0362. There are 62 homozygotes in gnomad4. There are 1720 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC8	NM_000082.4	c.1042-197A>G		intron_variant		ENST00000676185.1
ERCC8	NM_001007233.3	c.868-197A>G		intron_variant
ERCC8	NM_001290285.2	c.583-197A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC8	ENST00000676185.1	c.1042-197A>G		intron_variant			NM_000082.4	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3665 AN: 152202 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00588

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0374

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0240 AC: 3658 AN: 152320 Hom.: 62 Cov.: 33 AF XY: 0.0231 AC XY: 1720 AN XY: 74476

Gnomad4 AFR AF: 0.00584

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0374

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0351 Hom.: 120

Bravo AF: 0.0233

Asia WGS AF: 0.0100 AC: 35 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	15
Dann	Benign	0.92

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: rs4647128; hg19: chr5-60183544;