rs7325708

Positions:

• chr13-102847141-C-G

Variant summary

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

The NM_000123.4(ERCC5):​c.88+787C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,998 control chromosomes in the GnomAD database, including 5,196 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 0.25 (5196 hom., cov: 32)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.88+787C>G		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.1451-4977C>G		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.88+787C>G		intron_variant			NM_000123.4	ENSP00000498881	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37593 AN: 151880 Hom.: 5195 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.247 AC: 37618 AN: 151998 Hom.: 5196 Cov.: 32 AF XY: 0.247 AC XY: 18360 AN XY: 74328

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.245

Alfa AF: 0.212 Hom.: 483

Bravo AF: 0.266

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.7
DANN	Benign	0.56

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: rs7325708; hg19: chr13-103499491;