6-43759219-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+229948T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,012 control chromosomes in the GnomAD database, including 33,918 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 0.65 (33918 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+229948T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99373 AN: 151894 Hom.: 33904 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.654 AC: 99405 AN: 152012 Hom.: 33918 Cov.: 32 AF XY: 0.649 AC XY: 48247 AN XY: 74298

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.665

Alfa AF: 0.745 Hom.: 73500

Bravo AF: 0.640

Asia WGS AF: 0.478 AC: 1661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.014
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs866236; hg19: chr6-43726956;