rs1319052

chr19-45427963-G-A

Variant summary

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

The NM_001369412.1(ERCC1):c.-7-4582C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,020 control chromosomes in the GnomAD database, including 25,943 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 0.54 (25943 hom., cov: 32)
• Consequence: ERCC1 NM_001369412.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC1	NM_001369412.1	c.-7-4582C>T		intron_variant
ERCC1	NM_001369413.1	c.-7-4582C>T		intron_variant
ERCC1	NM_001369414.1	c.-7-4582C>T		intron_variant
ERCC1	NM_001369417.1	c.-7-4582C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC1	ENST00000423698.6	c.-7-4582C>T		intron_variant		2
ERCC1	ENST00000589214.1	c.-8+1006C>T		intron_variant		3
ERCC1	ENST00000592083.5	c.-7-4582C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82124 AN: 151902 Hom.: 25884 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.541 AC: 82245 AN: 152020 Hom.: 25943 Cov.: 32 AF XY: 0.543 AC XY: 40388 AN XY: 74314

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.511

Alfa AF: 0.425 Hom.: 3225

Bravo AF: 0.572

Asia WGS AF: 0.666 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.4
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1319052; hg19: chr19-45931221;