chr6-43982716-T-C

Position:

• chr6-43982716-T-C

Variant summary

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

The NM_001318876.2(POLR1C):​c.945+453445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,050 control chromosomes in the GnomAD database, including 15,905 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 0.46 (15905 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+453445T>C		intron_variant			NP_001305805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIRT	ENST00000687158.2	n.519+16502A>G		intron_variant
SCIRT	ENST00000687455.1	n.233+18327A>G		intron_variant
SCIRT	ENST00000687843.1	n.592+16502A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69234 AN: 151932 Hom.: 15900 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.456 AC: 69280 AN: 152050 Hom.: 15905 Cov.: 33 AF XY: 0.458 AC XY: 34013 AN XY: 74342

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.493

Alfa AF: 0.305 Hom.: 752

Bravo AF: 0.459

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.7
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4416670; hg19: chr6-43950453;