rs6900017

Positions:

• chr6-43790748-C-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+261477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,158 control chromosomes in the GnomAD database, including 1,704 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 0.13 (1704 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+261477C>T		intron_variant			NP_001305805.1
		n.43790748C>T		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19848 AN: 152040 Hom.: 1701 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.131 AC: 19866 AN: 152158 Hom.: 1704 Cov.: 32 AF XY: 0.130 AC XY: 9671 AN XY: 74416

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0875

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0876 Hom.: 1312

Bravo AF: 0.136

Asia WGS AF: 0.169 AC: 589 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	3.1
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6900017; hg19: chr6-43758485;