6-43770044-C-T

Position:

• chr6-43770044-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+240773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 294,866 control chromosomes in the GnomAD database, including 28 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 0.0069 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (10 hom.)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+240773C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1047 AN: 152100 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00535

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00634 AC: 904 AN: 142650 Hom.: 10 AF XY: 0.00602 AC XY: 423 AN XY: 70212

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.00215

Gnomad4 EAS exome AF: 0.0227

Gnomad4 SAS exome AF: 0.0261

Gnomad4 FIN exome AF: 0.000756

Gnomad4 NFE exome AF: 0.00423

Gnomad4 OTH exome AF: 0.00635

GnomAD4 genome AF: 0.00686 AC: 1044 AN: 152216 Hom.: 18 Cov.: 33 AF XY: 0.00712 AC XY: 530 AN XY: 74432

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.0428

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00535

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.000958 Hom.: 0

Bravo AF: 0.00618

Asia WGS AF: 0.0330 AC: 115 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79469752; hg19: chr6-43737781;