rs3212985

Positions:

• chr19-45409828-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012099.3(POLR1G):​c.*327C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 706,458 control chromosomes in the GnomAD database, including 14,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2446 hom., cov: 30)
  • Exomes 𝑓: 0.19 (11646 hom.)
• Consequence: POLR1G NM_012099.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.184

Genes affected

POLR1G (HGNC:24219): (RNA polymerase I subunit G) Enables RNA binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within rRNA transcription. Located in cytosol; mitochondrion; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-45409828-C-G is Benign according to our data. Variant chr19-45409828-C-G is described in ClinVar as [Benign]. Clinvar id is 1236680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1G	NM_012099.3	c.*327C>G		3_prime_UTR_variant	3/3	ENST00000309424.8	NP_036231.1
ERCC1	NM_001983.4	c.844-103G>C		intron_variant		ENST00000300853.8	NP_001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1G	ENST00000309424.8	c.*327C>G		3_prime_UTR_variant	3/3	1	NM_012099.3	ENSP00000310966.3
ERCC1	ENST00000300853.8	c.844-103G>C		intron_variant		1	NM_001983.4	ENSP00000300853.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24750 AN: 151098 Hom.: 2449 Cov.: 30

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.193 AC: 107326 AN: 555256 Hom.: 11646 Cov.: 0 AF XY: 0.197 AC XY: 59162 AN XY: 299624

Gnomad4 AFR exome AF: 0.0818

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.0106

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.164 AC: 24743 AN: 151202 Hom.: 2446 Cov.: 30 AF XY: 0.162 AC XY: 11956 AN XY: 73836

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.173

Alfa AF: 0.189 Hom.: 356

Bravo AF: 0.156

Asia WGS AF: 0.0920 AC: 324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3212985; hg19: chr19-45913086;