chr6-43837625-T-A

Position:

• chr6-43837625-T-A

Variant summary

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

The NM_001318876.2(POLR1C):​c.945+308354T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,120 control chromosomes in the GnomAD database, including 29,256 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 0.59 (29256 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+308354T>A		intron_variant			NP_001305805.1
LOC105375069	XR_001744130.1	n.675+259A>T		intron_variant
LOC105375070	XR_007059588.1	n.193-4886T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283573	ENST00000637813.1	n.366-4886T>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90074 AN: 152002 Hom.: 29252 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.592 AC: 90106 AN: 152120 Hom.: 29256 Cov.: 33 AF XY: 0.597 AC XY: 44400 AN XY: 74374

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.609

Alfa AF: 0.633 Hom.: 4003

Bravo AF: 0.582

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.3
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs744103; hg19: chr6-43805362;