6-43517545-C-T

Variant names:

• chr6-43517545-C-T
• rs2227301
• NM_203290.4:c.141+168C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_203290.4(POLR1C):​c.141+168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,750 control chromosomes in the GnomAD database, including 3,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3105 hom., cov: 31)
• Consequence: POLR1C NM_203290.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.761

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-43517545-C-T is Benign according to our data. Variant chr6-43517545-C-T is described in ClinVar as [Benign]. Clinvar id is 1277590.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1C	NM_203290.4	c.141+168C>T		intron_variant	Intron 2 of 8	ENST00000642195.1	NP_976035.1
POLR1C	NM_001318876.2	c.141+168C>T		intron_variant	Intron 2 of 8		NP_001305805.1
POLR1C	NM_001363658.2	c.141+168C>T		intron_variant	Intron 2 of 9		NP_001350587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1C	ENST00000642195.1	c.141+168C>T		intron_variant	Intron 2 of 8		NM_203290.4	ENSP00000496044.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27014 AN: 151630 Hom.: 3100 Cov.: 31

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.178 AC: 27019 AN: 151750 Hom.: 3105 Cov.: 31 AF XY: 0.183 AC XY: 13561 AN XY: 74104

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.171

Alfa AF: 0.223 Hom.: 1897

Bravo AF: 0.166

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2227301; hg19: chr6-43485283;