chr19-45427963-G-A

Variant names:

• chr19-45427963-G-A
• rs1319052
• NM_001369412.1:c.-7-4582C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.8).
• 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 rank	MANE	Protein	UniProt
ERCC1	NM_001369412.1	c.-7-4582C>T		intron_variant	Intron 1 of 9		NP_001356341.1
ERCC1	NM_001369413.1	c.-7-4582C>T		intron_variant	Intron 2 of 10		NP_001356342.1
ERCC1	NM_001369414.1	c.-7-4582C>T		intron_variant	Intron 2 of 10		NP_001356343.1
ERCC1	NM_001369417.1	c.-7-4582C>T		intron_variant	Intron 2 of 9		NP_001356346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC1	ENST00000592083.5	c.-7-4582C>T		intron_variant	Intron 2 of 8	5		ENSP00000467183.1
ERCC1	ENST00000423698.6	c.-7-4582C>T		intron_variant	Intron 1 of 8	2		ENSP00000394875.2
ERCC1	ENST00000589214.1	c.-8+1006C>T		intron_variant	Intron 1 of 3	3		ENSP00000465524.1

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

African (AFR) AF: 0.857 AC: 35567 AN: 41516

American (AMR) AF: 0.594 AC: 9058 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1309 AN: 3466

East Asian (EAS) AF: 0.739 AC: 3818 AN: 5168

South Asian (SAS) AF: 0.536 AC: 2588 AN: 4832

European-Finnish (FIN) AF: 0.360 AC: 3794 AN: 10538

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24517 AN: 67940

Other (OTH) AF: 0.511 AC: 1082 AN: 2116

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
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1319052; hg19: chr19-45931221;