rs12208152

chr6-43768243-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001318876.2(POLR1C):c.945+238972C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 152,134 control chromosomes in the GnomAD database, including 52 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 0.022 (52 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0223 (3390/152134) while in subpopulation NFE AF= 0.0345 (2348/67980). AF 95% confidence interval is 0.0334. There are 52 homozygotes in gnomad4. There are 1574 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 52 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+238972C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3389 AN: 152016 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0223 AC: 3390 AN: 152134 Hom.: 52 Cov.: 32 AF XY: 0.0212 AC XY: 1574 AN XY: 74358

Gnomad4 AFR AF: 0.00598

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0328 Hom.: 54

Bravo AF: 0.0217

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.3
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12208152; hg19: chr6-43735980;