6-43858890-C-T

Position:

• chr6-43858890-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001318876.2(POLR1C):​c.945+329619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,044 control chromosomes in the GnomAD database, including 29,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.61 (29476 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.773

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+329619C>T		intron_variant			NP_001305805.1
		n.43858890C>T		intergenic_region
LOC105375070	XR_007059588.1	n.315+16257C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92553 AN: 151926 Hom.: 29428 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.609 AC: 92661 AN: 152044 Hom.: 29476 Cov.: 32 AF XY: 0.615 AC XY: 45731 AN XY: 74320

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.604

Alfa AF: 0.529 Hom.: 44389

Bravo AF: 0.612

Asia WGS AF: 0.684 AC: 2376 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

not provided

Department of Ophthalmology and Visual Sciences Kyoto University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs943080; hg19: chr6-43826627;