rs833052

Positions:

• chr6-43755598-A-C
• chr6-43755598-A-G
• chr6-43755598-A-T

Variant summary

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

The NM_001318876.2(POLR1C):​c.945+226327A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,228 control chromosomes in the GnomAD database, including 59,177 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 0.88 (59177 hom., cov: 31)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

Genes affected

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+226327A>C		intron_variant			NP_001305805.1
		n.43755598A>C		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133808 AN: 152110 Hom.: 59113 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.880 AC: 133925 AN: 152228 Hom.: 59177 Cov.: 31 AF XY: 0.877 AC XY: 65268 AN XY: 74422

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.877

Alfa AF: 0.871 Hom.: 54021

Bravo AF: 0.884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs833052; hg19: chr6-43723335;