6-43768759-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001318876.2(POLR1C):​c.945+239488T>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 151,804 control chromosomes in the GnomAD database, including 28,233 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 ( 28233 hom., cov: 31)

Consequence

POLR1C
NM_001318876.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.681
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POLR1CNM_001318876.2 linkuse as main transcriptc.945+239488T>C intron_variant NP_001305805.1 O15160-2
use as main transcriptn.43768759T>C intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes
AF:
0.597
AC:
90620
AN:
151686
Hom.:
28203
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.789
Gnomad AMI
AF:
0.279
Gnomad AMR
AF:
0.614
Gnomad ASJ
AF:
0.538
Gnomad EAS
AF:
0.724
Gnomad SAS
AF:
0.555
Gnomad FIN
AF:
0.446
Gnomad MID
AF:
0.538
Gnomad NFE
AF:
0.501
Gnomad OTH
AF:
0.615
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.598
AC:
90708
AN:
151804
Hom.:
28233
Cov.:
31
AF XY:
0.595
AC XY:
44145
AN XY:
74180
show subpopulations
Gnomad4 AFR
AF:
0.789
Gnomad4 AMR
AF:
0.613
Gnomad4 ASJ
AF:
0.538
Gnomad4 EAS
AF:
0.725
Gnomad4 SAS
AF:
0.552
Gnomad4 FIN
AF:
0.446
Gnomad4 NFE
AF:
0.501
Gnomad4 OTH
AF:
0.615
Alfa
AF:
0.538
Hom.:
16589
Bravo
AF:
0.623
Asia WGS
AF:
0.611
AC:
2124
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
16
DANN
Benign
0.58

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1005230; hg19: chr6-43736496; API