rs699946

chr6-43764932-A-G

Variant summary

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

The NM_001318876.2(POLR1C):c.945+235661A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,852 control chromosomes in the GnomAD database, including 3,329 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 0.20 (3329 hom., cov: 31)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+235661A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30930 AN: 151732 Hom.: 3324 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.204 AC: 30946 AN: 151852 Hom.: 3329 Cov.: 31 AF XY: 0.205 AC XY: 15206 AN XY: 74216

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.218

Alfa AF: 0.202 Hom.: 6135

Bravo AF: 0.214

Asia WGS AF: 0.277 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.25
Dann	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs699946; hg19: chr6-43732669;