rs9472138

Positions:

• chr6-43844025-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+314754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,154 control chromosomes in the GnomAD database, including 4,787 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 0.24 (4787 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+314754C>T		intron_variant			NP_001305805.1
		n.43844025C>T		intergenic_region
LOC105375070	XR_007059588.1	n.315+1392C>T		intron_variant
LOC105375070	XR_007059589.1	n.316-1251C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37071 AN: 152038 Hom.: 4784 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.244 AC: 37097 AN: 152154 Hom.: 4787 Cov.: 32 AF XY: 0.243 AC XY: 18103 AN XY: 74380

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.267

Alfa AF: 0.273 Hom.: 13753

Bravo AF: 0.234

Asia WGS AF: 0.182 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9472138; hg19: chr6-43811762;