rs3793784

Positions:

• chr10-49539493-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277059.2(ERCC6):​c.-76C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,182 control chromosomes in the GnomAD database, including 8,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (8399 hom., cov: 32)
  • Exomes 𝑓: 0.36 (11 hom.)
• Consequence: ERCC6 NM_001277059.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1 O:2
• Conservation: PhyloP100: 2.02

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-49539493-G-C is Benign according to our data. Variant chr10-49539493-G-C is described in ClinVar as [Benign]. Clinvar id is 1709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC6	NM_001277059.2	c.-76C>G		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC6	ENST00000462247.1	c.-76C>G		5_prime_UTR_variant	1/3	3
ERCC6	ENST00000515869.1	c.-76C>G		5_prime_UTR_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45505 AN: 151916 Hom.: 8408 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.358 AC: 53 AN: 148 Hom.: 11 Cov.: 0 AF XY: 0.349 AC XY: 37 AN XY: 106

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.299 AC: 45479 AN: 152034 Hom.: 8399 Cov.: 32 AF XY: 0.297 AC XY: 22064 AN XY: 74314

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.318

Alfa AF: 0.346 Hom.: 1371

Bravo AF: 0.285

Asia WGS AF: 0.276 AC: 964 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

LUNG CANCER, SUSCEPTIBILITY TO Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jan 01, 2008

- -

Age related macular degeneration 5 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 08, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3793784; hg19: chr10-50747539;