19-45478557-G-T

Variant names:

• chr19-45478557-G-T
• rs6509214
• ENST00000899224.1:c.-8+179C>A

Variant summary

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

The ENST00000423698.6(ERCC1):​c.-8+179C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,106 control chromosomes in the GnomAD database, including 10,594 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 0.37 (10594 hom., cov: 33)
• Consequence: ERCC1 ENST00000423698.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• Publications: 15 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

TRU-TCA1-1 (HGNC:12348):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000423698.6. 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.-8+179C>A		intron	N/A	ENSP00000569283.1
	ERCC1	ENST00000899225.1		c.-8+179C>A		intron	N/A	ENSP00000569284.1
	ERCC1	ENST00000423698.6	TSL:2	c.-8+179C>A		intron	N/A	ENSP00000394875.2	P07992-4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56347 AN: 151988 Hom.: 10581 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.371 AC: 56409 AN: 152106 Hom.: 10594 Cov.: 33 AF XY: 0.377 AC XY: 28041 AN XY: 74344

African (AFR) AF: 0.395 AC: 16393 AN: 41504

American (AMR) AF: 0.392 AC: 5992 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1136 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2567 AN: 5188

South Asian (SAS) AF: 0.506 AC: 2441 AN: 4824

European-Finnish (FIN) AF: 0.330 AC: 3484 AN: 10568

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23215 AN: 67958

Other (OTH) AF: 0.370 AC: 781 AN: 2112

Alfa AF: 0.348 Hom.: 7894

Bravo AF: 0.377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.34
DANN	Benign	0.44
PhyloP100		-0.92
PromoterAI		0.044	Neutral
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: rs6509214; hg19: chr19-45981815;