chr19-45411780-T-C

Variant names:

• chr19-45411780-T-C
• rs3212981
• NM_001983.4:c.843+1897A>G

Variant summary

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

The NM_001983.4(ERCC1):​c.843+1897A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,002 control chromosomes in the GnomAD database, including 5,867 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 0.28 (5867 hom., cov: 29)
• Consequence: ERCC1 NM_001983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 8 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC1	NM_001983.4	c.843+1897A>G		intron_variant	Intron 9 of 9	ENST00000300853.8	NP_001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC1	ENST00000300853.8	c.843+1897A>G		intron_variant	Intron 9 of 9	1	NM_001983.4	ENSP00000300853.3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41593 AN: 150884 Hom.: 5855 Cov.: 29

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.276 AC: 41641 AN: 151002 Hom.: 5867 Cov.: 29 AF XY: 0.277 AC XY: 20436 AN XY: 73722

African (AFR) AF: 0.303 AC: 12451 AN: 41150

American (AMR) AF: 0.355 AC: 5383 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 847 AN: 3452

East Asian (EAS) AF: 0.310 AC: 1565 AN: 5048

South Asian (SAS) AF: 0.299 AC: 1428 AN: 4768

European-Finnish (FIN) AF: 0.231 AC: 2405 AN: 10398

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16601 AN: 67722

Other (OTH) AF: 0.275 AC: 578 AN: 2102

Alfa AF: 0.250 Hom.: 607

Bravo AF: 0.286

Asia WGS AF: 0.319 AC: 1112 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.072
DANN	Benign	0.15
PhyloP100		-2.6
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: rs3212981; hg19: chr19-45915038;