rs7742824

Positions:

• chr6-44097574-G-A
• chr6-44097574-G-T

Variant summary

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

The NM_001318876.2(POLR1C):​c.946-344316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,316 control chromosomes in the GnomAD database, including 5,665 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 0.26 (5665 hom., cov: 28)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.946-344316G>A		intron_variant			NP_001305805.1
		n.44097574G>A		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39485 AN: 151200 Hom.: 5662 Cov.: 28

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.261 AC: 39509 AN: 151316 Hom.: 5665 Cov.: 28 AF XY: 0.259 AC XY: 19139 AN XY: 73928

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.263

Alfa AF: 0.221 Hom.: 1720

Bravo AF: 0.270

Asia WGS AF: 0.220 AC: 767 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.66
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7742824; hg19: chr6-44065311;