13-102845830-C-A

Variant summary

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

The NM_001204425.2(BIVM-ERCC5):c.1450+6027C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 253,814 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (257 hom., cov: 33)
  • Exomes 𝑓: 0.0086 (48 hom.)
• Consequence: BIVM-ERCC5 NM_001204425.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.66

Genes affected

BIVM-ERCC5 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 13-102845830-C-A is Benign according to our data. Variant chr13-102845830-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 369032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIVM-ERCC5	NM_001204425.2	c.1450+6027C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC5	ENST00000652613.1			upstream_gene_variant
ERCC5	ENST00000535557.5			upstream_gene_variant		5
ERCC5	ENST00000651002.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4906 AN: 152228 Hom.: 256 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00863 AC: 876 AN: 101468 Hom.: 48 Cov.: 0 AF XY: 0.00825 AC XY: 404 AN XY: 48966

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.00820

Gnomad4 ASJ exome AF: 0.0135

Gnomad4 EAS exome AF: 0.00668

Gnomad4 SAS exome AF: 0.00715

Gnomad4 FIN exome AF: 0.00213

Gnomad4 NFE exome AF: 0.000746

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0323 AC: 4916 AN: 152346 Hom.: 257 Cov.: 33 AF XY: 0.0312 AC XY: 2326 AN XY: 74504

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.000659 Hom.: 0

Bravo AF: 0.0363

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Xeroderma pigmentosum Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.7
Dann	Benign	0.78

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: rs4150248; hg19: chr13-103498180;