rs4150351

Variant names:

• chr13-102870617-A-C
• rs4150351
• NM_000123.4:c.2679-1581A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-102870617-A-C
• chr13-102870617-A-T

Variant summary

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

The NM_000123.4(ERCC5):​c.2679-1581A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,270 control chromosomes in the GnomAD database, including 1,528 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 (1528 hom., cov: 32)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2679-1581A>C		intron_variant	Intron 12 of 14	ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4041-1581A>C		intron_variant	Intron 20 of 22		NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2679-1581A>C		intron_variant	Intron 12 of 14		NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.4041-1581A>C		intron_variant	Intron 22 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.3354-1581A>C		intron_variant	Intron 21 of 23	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18067 AN: 152150 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.119 AC: 18059 AN: 152270 Hom.: 1528 Cov.: 32 AF XY: 0.116 AC XY: 8663 AN XY: 74438

African (AFR) AF: 0.0322 AC: 1339 AN: 41568

American (AMR) AF: 0.0895 AC: 1370 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5192

South Asian (SAS) AF: 0.0744 AC: 359 AN: 4826

European-Finnish (FIN) AF: 0.202 AC: 2140 AN: 10588

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12144 AN: 67996

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.131 Hom.: 796

Bravo AF: 0.107

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.36
PhyloP100		0.069
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: rs4150351; hg19: chr13-103522967;