13-102870962-C-T

Variant names:

• chr13-102870962-C-T
• rs4150355
• NM_000123.4:c.2679-1236C>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.2679-1236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,078 control chromosomes in the GnomAD database, including 7,223 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 0.29 (7223 hom., cov: 33)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 22 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 = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2679-1236C>T		intron_variant	Intron 12 of 14	ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4041-1236C>T		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.2679-1236C>T		intron_variant	Intron 12 of 14		NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.4041-1236C>T		intron_variant	Intron 22 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.3354-1236C>T		intron_variant	Intron 21 of 23	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43987 AN: 151960 Hom.: 7211 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.289 AC: 44018 AN: 152078 Hom.: 7223 Cov.: 33 AF XY: 0.291 AC XY: 21673 AN XY: 74356

African (AFR) AF: 0.141 AC: 5852 AN: 41466

American (AMR) AF: 0.258 AC: 3943 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3468

East Asian (EAS) AF: 0.183 AC: 948 AN: 5182

South Asian (SAS) AF: 0.363 AC: 1751 AN: 4824

European-Finnish (FIN) AF: 0.350 AC: 3701 AN: 10576

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25129 AN: 67978

Other (OTH) AF: 0.320 AC: 675 AN: 2110

Alfa AF: 0.346 Hom.: 15661

Bravo AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.52
PhyloP100		-1.0
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: rs4150355; hg19: chr13-103523312;