rs998584

Positions:

• chr6-43790159-C-A
• chr6-43790159-C-T

Variant summary

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

The NM_001318876.2(POLR1C):​c.945+260888C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,950 control chromosomes in the GnomAD database, including 14,752 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 0.42 (14752 hom., cov: 31)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+260888C>A		intron_variant			NP_001305805.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63275 AN: 151832 Hom.: 14742 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.417 AC: 63311 AN: 151950 Hom.: 14752 Cov.: 31 AF XY: 0.426 AC XY: 31602 AN XY: 74248

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.421

Alfa AF: 0.476 Hom.: 14787

Bravo AF: 0.403

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs998584; hg19: chr6-43757896;