chr6-44239013-G-A

Position:

• chr6-44239013-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318876.2(POLR1C):​c.946-202877G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,146 control chromosomes in the GnomAD database, including 2,315 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 0.15 (2315 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.946-202877G>A		intron_variant			NP_001305805.1
		n.44239013G>A		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23234 AN: 152028 Hom.: 2315 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.153 AC: 23232 AN: 152146 Hom.: 2315 Cov.: 32 AF XY: 0.157 AC XY: 11668 AN XY: 74374

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.152

Alfa AF: 0.178 Hom.: 3630

Bravo AF: 0.154

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.2
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: rs9472236; hg19: chr6-44206750;