rs4150276

Variant names:

• chr13-102854879-T-A
• rs4150276
• NM_000123.4:c.467+505T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000123.4(ERCC5):​c.467+505T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,066 control chromosomes in the GnomAD database, including 26,502 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 0.58 (26502 hom., cov: 32)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.467+505T>A		intron_variant	Intron 4 of 14	ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.1829+505T>A		intron_variant	Intron 12 of 22		NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.467+505T>A		intron_variant	Intron 4 of 14		NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.1829+505T>A		intron_variant	Intron 14 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.1142+505T>A		intron_variant	Intron 13 of 23	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88359 AN: 151948 Hom.: 26454 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.582 AC: 88458 AN: 152066 Hom.: 26502 Cov.: 32 AF XY: 0.578 AC XY: 42990 AN XY: 74346

African (AFR) AF: 0.663 AC: 27497 AN: 41470

American (AMR) AF: 0.423 AC: 6460 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2047 AN: 3472

East Asian (EAS) AF: 0.246 AC: 1275 AN: 5174

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4820

European-Finnish (FIN) AF: 0.623 AC: 6593 AN: 10578

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40358 AN: 67970

Other (OTH) AF: 0.566 AC: 1190 AN: 2102

Alfa AF: 0.595 Hom.: 3385

Bravo AF: 0.567

Asia WGS AF: 0.404 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.75
DANN	Benign	0.63
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4150276; hg19: chr13-103507229;