rs2066432

Positions:

• chr6-43966925-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+437654C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,934 control chromosomes in the GnomAD database, including 19,984 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 0.51 (19984 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

SCIRT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+437654C>T		intron_variant			NP_001305805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIRT	ENST00000687158.2	n.519+32293G>A		intron_variant
SCIRT	ENST00000687455.1	n.233+34118G>A		intron_variant
SCIRT	ENST00000687843.1	n.592+32293G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77051 AN: 151816 Hom.: 19972 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.507 AC: 77094 AN: 151934 Hom.: 19984 Cov.: 33 AF XY: 0.514 AC XY: 38184 AN XY: 74278

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.525

Alfa AF: 0.496 Hom.: 4763

Bravo AF: 0.516

Asia WGS AF: 0.678 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2066432; hg19: chr6-43934662;