chr6-43933447-T-C

Position:

• chr6-43933447-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+404176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,114 control chromosomes in the GnomAD database, including 7,165 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 0.30 (7165 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+404176T>C		intron_variant			NP_001305805.1
LINC01512	NR_024478.1	n.439-2917T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIRT	ENST00000687158.2	n.520-1271A>G		intron_variant
SCIRT	ENST00000687455.1	n.234-1271A>G		intron_variant
SCIRT	ENST00000687843.1	n.593-1271A>G		intron_variant
LINC01512	ENST00000691600.1	n.422-2917T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44873 AN: 151996 Hom.: 7135 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.295 AC: 44949 AN: 152114 Hom.: 7165 Cov.: 32 AF XY: 0.290 AC XY: 21541 AN XY: 74368

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.325

Alfa AF: 0.269 Hom.: 1761

Bravo AF: 0.312

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6923866; hg19: chr6-43901184;