chr19-45479115-T-G

Variant names:

• chr19-45479115-T-G
• rs12972892
• ENST00000899224.1:c.-387A>C

Variant summary

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

The ENST00000899224.1(ERCC1):​c.-387A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,176 control chromosomes in the GnomAD database, including 649 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 0.076 (649 hom., cov: 32)
• Consequence: ERCC1 ENST00000899224.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 4 publications found

Genes affected

ERCC1 (HGNC:3433): (ERCC excision repair 1, endonuclease non-catalytic subunit) The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]

ERCC1 Gene-Disease associations (from GenCC):

• cerebrooculofacioskeletal syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Cockayne syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• COFS syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000899224.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC1	ENST00000899224.1		c.-387A>C		upstream_gene	N/A	ENSP00000569283.1

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11637 AN: 152058 Hom.: 647 Cov.: 32

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0765 AC: 11635 AN: 152176 Hom.: 649 Cov.: 32 AF XY: 0.0799 AC XY: 5941 AN XY: 74396

African (AFR) AF: 0.0308 AC: 1278 AN: 41518

American (AMR) AF: 0.157 AC: 2396 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3472

East Asian (EAS) AF: 0.208 AC: 1075 AN: 5164

South Asian (SAS) AF: 0.131 AC: 633 AN: 4826

European-Finnish (FIN) AF: 0.0293 AC: 311 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5121 AN: 68002

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0636 Hom.: 60

Bravo AF: 0.0843

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.65
PhyloP100		-0.29
PromoterAI		-0.0048	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12972892; hg19: chr19-45982373;