6-43837071-G-C

Position:

• chr6-43837071-G-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+307800G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,028 control chromosomes in the GnomAD database, including 29,625 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 0.60 (29625 hom., cov: 31)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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]

ENSG00000283573 (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 = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+307800G>C		intron_variant			NP_001305805.1
LOC105375069	XR_001744130.1	n.676-60C>G		intron_variant
LOC105375070	XR_007059588.1	n.193-5440G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283573	ENST00000637813.1	n.366-5440G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90948 AN: 151910 Hom.: 29620 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.598 AC: 90984 AN: 152028 Hom.: 29625 Cov.: 31 AF XY: 0.603 AC XY: 44807 AN XY: 74304

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.617

Alfa AF: 0.521 Hom.: 1661

Bravo AF: 0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2396083; hg19: chr6-43804808;