rs873601

chr13-102875987-G-Achr13-102875987-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000123.4(ERCC5):c.*84G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,513,566 control chromosomes in the GnomAD database, including 371,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (29263 hom., cov: 33)
  • Exomes 𝑓: 0.70 (342074 hom.)
• Consequence: ERCC5 NM_000123.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0380

Genes affected

ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

BIVM-ERCC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-102875987-G-A is Benign according to our data. Variant chr13-102875987-G-A is described in ClinVar as [Benign]. Clinvar id is 310945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC5	NM_000123.4	c.*84G>A		3_prime_UTR_variant	15/15	ENST00000652225.2
BIVM-ERCC5	NM_001204425.2	c.*84G>A		3_prime_UTR_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC5	ENST00000652225.2	c.*84G>A		3_prime_UTR_variant	15/15		NM_000123.4	P1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90802 AN: 152046 Hom.: 29260 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.704 AC: 958649 AN: 1361402 Hom.: 342074 Cov.: 21 AF XY: 0.707 AC XY: 479955 AN XY: 678612

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.633

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.740

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.728

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.597 AC: 90830 AN: 152164 Hom.: 29263 Cov.: 33 AF XY: 0.597 AC XY: 44427 AN XY: 74394

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.613

Alfa AF: 0.697 Hom.: 63285

Bravo AF: 0.578

Asia WGS AF: 0.570 AC: 1984 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Xeroderma pigmentosum, group G Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.1
Dann	Benign	0.93

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: rs873601; hg19: chr13-103528337;