rs732321

Positions:

• chr13-102872604-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.2879+206A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 151,768 control chromosomes in the GnomAD database, including 1,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1353 hom., cov: 32)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.276

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:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]

ERCC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-102872604-A-C is Benign according to our data. Variant chr13-102872604-A-C is described in ClinVar as [Benign]. Clinvar id is 1275230.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2879+206A>C		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4241+206A>C		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2879+206A>C		intron_variant			NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.4241+206A>C		intron_variant		5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.3554+206A>C		intron_variant		5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15271 AN: 151650 Hom.: 1352 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0972

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

GnomAD4 genome AF: 0.101 AC: 15293 AN: 151768 Hom.: 1353 Cov.: 32 AF XY: 0.0995 AC XY: 7381 AN XY: 74184

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.0468

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0685

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.0842 Hom.: 121

Bravo AF: 0.105

Asia WGS AF: 0.0560 AC: 194 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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.67

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: rs732321; hg19: chr13-103524954;