rs4150386

Positions:

• chr13-102875178-A-C

Variant summary

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

The NM_000123.4(ERCC5):​c.2965-129A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,077,046 control chromosomes in the GnomAD database, including 6,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (628 hom., cov: 33)
  • Exomes 𝑓: 0.11 (6307 hom.)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.180

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-102875178-A-C is Benign according to our data. Variant chr13-102875178-A-C is described in ClinVar as [Benign]. Clinvar id is 1268900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2965-129A>C		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4327-129A>C		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2965-129A>C		intron_variant			NM_000123.4	ENSP00000498881	P1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12448 AN: 152182 Hom.: 628 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0864

GnomAD4 exome AF: 0.110 AC: 101661 AN: 924746 Hom.: 6307 AF XY: 0.109 AC XY: 51238 AN XY: 468542

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.0672

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.00846

Gnomad4 SAS exome AF: 0.0747

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.0992

GnomAD4 genome AF: 0.0817 AC: 12447 AN: 152300 Hom.: 628 Cov.: 33 AF XY: 0.0802 AC XY: 5972 AN XY: 74466

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00810

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0860

Alfa AF: 0.0876 Hom.: 82

Bravo AF: 0.0781

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
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: rs4150386; hg19: chr13-103527528;