rs699947

Positions:

• chr6-43768652-A-C
• chr6-43768652-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001318876.2(POLR1C):​c.945+239381A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,102 control chromosomes in the GnomAD database, including 28,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.60 (28280 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.03

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-43768652-A-C is Benign according to our data. Variant chr6-43768652-A-C is described in ClinVar as [Benign]. Clinvar id is 12224.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+239381A>C		intron_variant			NP_001305805.1
		n.43768652A>C		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90793 AN: 151984 Hom.: 28251 Cov.: 33

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.597 AC: 90880 AN: 152102 Hom.: 28280 Cov.: 33 AF XY: 0.595 AC XY: 44239 AN XY: 74346

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.616

Alfa AF: 0.503 Hom.: 3587

Bravo AF: 0.623

Asia WGS AF: 0.611 AC: 2124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Atherosclerosis, susceptibility to Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Dec 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs699947; hg19: chr6-43736389;