13-102866494-C-T

Position:

• chr13-102866494-C-T

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.2319+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,606,480 control chromosomes in the GnomAD database, including 45,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4077 hom., cov: 33)
  • Exomes 𝑓: 0.23 (41355 hom.)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.99

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=-0.92).
• BP6: Variant 13-102866494-C-T is Benign according to our data. Variant chr13-102866494-C-T is described in ClinVar as [Benign]. Clinvar id is 1245173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2319+113C>T		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.3681+113C>T		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2319+113C>T		intron_variant			NM_000123.4	ENSP00000498881	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34105 AN: 152044 Hom.: 4073 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.232 AC: 337927 AN: 1454318 Hom.: 41355 Cov.: 32 AF XY: 0.235 AC XY: 169732 AN XY: 723498

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.224 AC: 34112 AN: 152162 Hom.: 4077 Cov.: 33 AF XY: 0.226 AC XY: 16838 AN XY: 74372

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.227

Alfa AF: 0.224 Hom.: 3049

Bravo AF: 0.229

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.92
CADD	Benign	0.019
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3759500; hg19: chr13-103518844;