rs3212930

Positions:

• chr19-45424352-A-G

Variant summary

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

The ENST00000589165.5(ERCC1):​c.-537T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,432 control chromosomes in the GnomAD database, including 2,611 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 0.17 (2607 hom., cov: 32)
  • Exomes 𝑓: 0.19 (4 hom.)
• Consequence: ERCC1 ENST00000589165.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC1	NM_001369412.1	c.-7-971T>C		intron_variant
ERCC1	NM_001369413.1	c.-7-971T>C		intron_variant
ERCC1	NM_001369414.1	c.-7-971T>C		intron_variant
ERCC1	NM_001369417.1	c.-7-971T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC1	ENST00000589165.5	c.-537T>C		5_prime_UTR_variant	1/10	5		P1
ERCC1	ENST00000423698.6	c.-7-971T>C		intron_variant		2
ERCC1	ENST00000589214.1	c.-7-971T>C		intron_variant		3
ERCC1	ENST00000592083.5	c.-7-971T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26131 AN: 152086 Hom.: 2609 Cov.: 32

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.193 AC: 44 AN: 228 Hom.: 4 Cov.: 0 AF XY: 0.154 AC XY: 20 AN XY: 130

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.172 AC: 26135 AN: 152204 Hom.: 2607 Cov.: 32 AF XY: 0.172 AC XY: 12792 AN XY: 74400

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.194

Alfa AF: 0.183 Hom.: 319

Bravo AF: 0.177

Asia WGS AF: 0.122 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.1
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3212930; hg19: chr19-45927610;