rs59260042

chr6-43770037-C-Achr6-43770037-C-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+240766C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 288,680 control chromosomes in the GnomAD database, including 421 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 0.038 (380 hom., cov: 33)
  • Exomes 𝑓: 0.0068 (41 hom.)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+240766C>A		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5842 AN: 152074 Hom.: 381 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00209

Gnomad OTH AF: 0.0354

GnomAD4 exome AF: 0.00682 AC: 931 AN: 136486 Hom.: 41 AF XY: 0.00574 AC XY: 385 AN XY: 67058

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.0000605

Gnomad4 SAS exome AF: 0.000890

Gnomad4 FIN exome AF: 0.000121

Gnomad4 NFE exome AF: 0.00200

Gnomad4 OTH exome AF: 0.0158

GnomAD4 genome AF: 0.0385 AC: 5853 AN: 152194 Hom.: 380 Cov.: 33 AF XY: 0.0381 AC XY: 2839 AN XY: 74428

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00209

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.00140 Hom.: 3

Bravo AF: 0.0442

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.6
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59260042; hg19: chr6-43737774;