rs6933958

Positions:

• chr6-43855952-T-C

Variant summary

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

The NM_001318876.2(POLR1C):​c.945+326681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,850 control chromosomes in the GnomAD database, including 7,273 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 0.31 (7273 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+326681T>C		intron_variant			NP_001305805.1
		n.43855952T>C		intergenic_region
LOC105375070	XR_007059588.1	n.315+13319T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46478 AN: 151730 Hom.: 7262 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.306 AC: 46514 AN: 151850 Hom.: 7273 Cov.: 32 AF XY: 0.312 AC XY: 23192 AN XY: 74218

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.309

Alfa AF: 0.284 Hom.: 13000

Bravo AF: 0.309

Asia WGS AF: 0.357 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6933958; hg19: chr6-43823689;