6-43759293-G-T

Position:

• chr6-43759293-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+230022G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,060 control chromosomes in the GnomAD database, including 40,481 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 0.72 (40481 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+230022G>T		intron_variant			NP_001305805.1
		n.43759293G>T		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110111 AN: 151942 Hom.: 40458 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.725 AC: 110170 AN: 152060 Hom.: 40481 Cov.: 32 AF XY: 0.718 AC XY: 53398 AN XY: 74326

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.718

Alfa AF: 0.758 Hom.: 42363

Bravo AF: 0.720

Asia WGS AF: 0.485 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs833057; hg19: chr6-43727030;