rs4150375

Positions:

• chr13-102874767-A-G
• chr13-102874767-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.2965-540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,184 control chromosomes in the GnomAD database, including 1,536 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 (1536 hom., cov: 33)
  • Exomes 𝑓: 0.11 (18 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2965-540A>G		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4327-540A>G		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2965-540A>G		intron_variant			NM_000123.4	ENSP00000498881	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18599 AN: 152066 Hom.: 1537 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.109 AC: 225 AN: 2064 Hom.: 18 Cov.: 0 AF XY: 0.0942 AC XY: 116 AN XY: 1232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.474

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0837

Gnomad4 OTH exome AF: 0.0588

GnomAD4 genome AF: 0.122 AC: 18611 AN: 152184 Hom.: 1536 Cov.: 33 AF XY: 0.126 AC XY: 9390 AN XY: 74390

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0841

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0370 Hom.: 23

Bravo AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.66
DANN	Benign	0.31

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: rs4150375; hg19: chr13-103527117;