Variant chr6-43997428-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001318876.2(POLR1C):c.946-444462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,092 control chromosomes in the GnomAD database, including 13,667 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 0.35 ( 13666 hom., cov: 32)

Exomes 𝑓: 0.15 ( 1 hom. )

Consequence

POLR1C
NM_001318876.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

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]

POLR1C links:

SCIRT (HGNC:):

SCIRT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-444462T>C	intron_variant	NP_001305805.1	O15160-2
SCIRT	NR_125864.1 linkuse as main transcript	n.647-120A>G	intron_variant
SCIRT	NR_125865.1 linkuse as main transcript	n.431-120A>G	intron_variant
LOC124901321	XR_007059591.1 linkuse as main transcript	n.43-1523T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
SCIRT	ENST00000422059.5 linkuse as main transcript	n.647-120A>G	intron_variant	2
SCIRT	ENST00000607590.1 linkuse as main transcript	n.430-120A>G	intron_variant	3
SCIRT	ENST00000652850.1 linkuse as main transcript	n.450-120A>G	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52534

AN:

151902

Hom.:

13612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.320

GnomAD4 exome

AF:

0.153

AC:

AN:

Hom.:

AF XY:

0.196

AC XY:

AN XY:

show subpopulations

Gnomad4 AMR exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.346

AC:

52657

AN:

152020

Hom.:

13666

Cov.:

AF XY:

0.346

AC XY:

25698

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.726

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.194

Hom.:

7554

Bravo

AF:

0.373

Asia WGS

AF:

0.416

AC:

1449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over