rs4150351

chr13-102870617-A-Cchr13-102870617-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000123.4(ERCC5):c.2679-1581A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,270 control chromosomes in the GnomAD database, including 1,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1528 hom., cov: 32)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC5	NM_000123.4	c.2679-1581A>C		intron_variant		ENST00000652225.2
BIVM-ERCC5	NM_001204425.2	c.4041-1581A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC5	ENST00000652225.2	c.2679-1581A>C		intron_variant			NM_000123.4	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18067 AN: 152150 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.0985

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18059 AN: 152270 Hom.: 1528 Cov.: 32 AF XY: 0.116 AC XY: 8663 AN XY: 74438

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.0895

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.128 Hom.: 696

Bravo AF: 0.107

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.0
Dann	Benign	0.36

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: rs4150351; hg19: chr13-103522967;