chr6-43957789-A-G

Position:

• chr6-43957789-A-G

Variant summary

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

The NM_001318876.2(POLR1C):​c.945+428518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,070 control chromosomes in the GnomAD database, including 14,850 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 0.44 (14850 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+428518A>G		intron_variant			NP_001305805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIRT	ENST00000687158.2	n.520-25613T>C		intron_variant
SCIRT	ENST00000687455.1	n.234-25613T>C		intron_variant
SCIRT	ENST00000687843.1	n.593-25613T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66513 AN: 151952 Hom.: 14838 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.438 AC: 66539 AN: 152070 Hom.: 14850 Cov.: 32 AF XY: 0.438 AC XY: 32565 AN XY: 74332

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.422

Alfa AF: 0.0773 Hom.: 2618

Bravo AF: 0.440

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.77
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4513773; hg19: chr6-43925526;