rs833062

chr6-43769792-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001318876.2(POLR1C):c.945+240521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 152,180 control chromosomes in the GnomAD database, including 32 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 0.015 (32 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2245/152180) while in subpopulation NFE AF= 0.0211 (1432/67986). AF 95% confidence interval is 0.0202. There are 32 homozygotes in gnomad4. There are 1166 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+240521T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2246 AN: 152062 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00878

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.0148 AC: 2245 AN: 152180 Hom.: 32 Cov.: 33 AF XY: 0.0157 AC XY: 1166 AN XY: 74392

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.0174 Hom.: 12

Bravo AF: 0.0127

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.46
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs833062; hg19: chr6-43737529;