chr6-43751654-G-T

Position:

• chr6-43751654-G-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+222383G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,092 control chromosomes in the GnomAD database, including 8,386 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 0.33 (8386 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+222383G>T		intron_variant			NP_001305805.1
		n.43751654G>T		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49938 AN: 151974 Hom.: 8373 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.329 AC: 49996 AN: 152092 Hom.: 8386 Cov.: 33 AF XY: 0.326 AC XY: 24260 AN XY: 74342

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.317

Alfa AF: 0.349 Hom.: 12459

Bravo AF: 0.316

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9394963; hg19: chr6-43719391;