19-45459541-A-G

Position:

• chr19-45459541-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000423698.6(ERCC1):​c.-8+19195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,990 control chromosomes in the GnomAD database, including 8,680 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 0.33 (8680 hom., cov: 31)
• Consequence: ERCC1 ENST00000423698.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.45459541A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC1	ENST00000423698.6	c.-8+19195T>C		intron_variant		2		ENSP00000394875.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49363 AN: 151872 Hom.: 8655 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.325 AC: 49427 AN: 151990 Hom.: 8680 Cov.: 31 AF XY: 0.330 AC XY: 24534 AN XY: 74300

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.304

Alfa AF: 0.266 Hom.: 11426

Bravo AF: 0.332

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10415949; hg19: chr19-45962799;