rs4253160

chr10-49485920-T-A

Variant summary

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

The NM_000124.4(ERCC6):c.1822-2404A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,122 control chromosomes in the GnomAD database, including 9,368 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 0.32 (9368 hom., cov: 32)
• Consequence: ERCC6 NM_000124.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC6	NM_000124.4	c.1822-2404A>T		intron_variant		ENST00000355832.10
ERCC6	NM_001346440.2	c.1822-2404A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC6	ENST00000355832.10	c.1822-2404A>T		intron_variant		1	NM_000124.4	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47963 AN: 152004 Hom.: 9375 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.315 AC: 47941 AN: 152122 Hom.: 9368 Cov.: 32 AF XY: 0.313 AC XY: 23288 AN XY: 74330

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.333

Alfa AF: 0.361 Hom.: 1404

Bravo AF: 0.300

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.7
Dann	Benign	0.72

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: rs4253160; hg19: chr10-50693966;