chr10-49514779-T-G

Position:

• chr10-49514779-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000124.4(ERCC6):​c.1398-8767A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 152,280 control chromosomes in the GnomAD database, including 688 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 0.085 (688 hom., cov: 32)
• Consequence: ERCC6 NM_000124.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC6	NM_000124.4	c.1398-8767A>C		intron_variant		ENST00000355832.10
ERCC6	NM_001346440.2	c.1398-8767A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC6	ENST00000355832.10	c.1398-8767A>C		intron_variant		1	NM_000124.4	P1

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12910 AN: 152162 Hom.: 684 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0778

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

GnomAD4 genome AF: 0.0849 AC: 12925 AN: 152280 Hom.: 688 Cov.: 32 AF XY: 0.0886 AC XY: 6599 AN XY: 74462

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.0841

Alfa AF: 0.0854 Hom.: 146

Bravo AF: 0.0879

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.83

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: rs4253079; hg19: chr10-50722825;