rs4150383

Variant names:

• chr13-102874880-G-A
• rs4150383
• NM_000123.4:c.2965-427G>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.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
• Publications: 17 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2965-427G>A		intron_variant	Intron 14 of 14	ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4327-427G>A		intron_variant	Intron 22 of 22		NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2965-427G>A		intron_variant	Intron 14 of 14		NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.4327-427G>A		intron_variant	Intron 24 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.3640-427G>A		intron_variant	Intron 23 of 23	5		ENSP00000492684.1

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

African (AFR) AF: 0.105 AC: 9 AN: 86

American (AMR) AF: 0.104 AC: 182 AN: 1748

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 15 AN: 208

East Asian (EAS) AF: 0.0399 AC: 23 AN: 576

South Asian (SAS) AF: 0.140 AC: 221 AN: 1582

European-Finnish (FIN) AF: 0.135 AC: 52 AN: 386

Middle Eastern (MID) AF: 0.136 AC: 3 AN: 22

European-Non Finnish (NFE) AF: 0.162 AC: 1331 AN: 8200

Other (OTH) AF: 0.143 AC: 86 AN: 600

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

African (AFR) AF: 0.0997 AC: 4143 AN: 41542

American (AMR) AF: 0.120 AC: 1830 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0870 AC: 302 AN: 3470

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5186

South Asian (SAS) AF: 0.154 AC: 740 AN: 4814

European-Finnish (FIN) AF: 0.180 AC: 1903 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12032 AN: 67998

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.160 Hom.: 6542

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
PhyloP100		-2.1
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: rs4150383; hg19: chr13-103527230;