rs4150383

Positions:

• chr13-102874880-G-A

Variant summary

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

The NM_000123.4(ERCC5):​c.2965-427G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 165,618 control chromosomes in the GnomAD database, including 1,839 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 0.14 (1678 hom., cov: 33)
  • Exomes 𝑓: 0.14 (161 hom.)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2965-427G>A		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4327-427G>A		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2965-427G>A		intron_variant			NM_000123.4	ENSP00000498881	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21729 AN: 152092 Hom.: 1678 Cov.: 33

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.143 AC: 1922 AN: 13408 Hom.: 161 Cov.: 0 AF XY: 0.140 AC XY: 1021 AN XY: 7298

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0721

Gnomad4 EAS exome AF: 0.0399

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.143 AC: 21728 AN: 152210 Hom.: 1678 Cov.: 33 AF XY: 0.143 AC XY: 10606 AN XY: 74412

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.131

Alfa AF: 0.163 Hom.: 2917

Bravo AF: 0.134

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.66

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: rs4150383; hg19: chr13-103527230;