chr6-43796814-C-T

Position:

• chr6-43796814-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+267543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,898 control chromosomes in the GnomAD database, including 14,348 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 0.41 (14348 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+267543C>T		intron_variant			NP_001305805.1
		n.43796814C>T		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61589 AN: 151780 Hom.: 14337 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.406 AC: 61619 AN: 151898 Hom.: 14348 Cov.: 32 AF XY: 0.413 AC XY: 30691 AN XY: 74230

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.432

Alfa AF: 0.474 Hom.: 35300

Bravo AF: 0.392

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1358980; hg19: chr6-43764551;