6-43770068-A-C

Position:

• chr6-43770068-A-C

Variant summary

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

The NM_001318876.2(POLR1C):​c.945+240797A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 293,628 control chromosomes in the GnomAD database, including 418 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 0.045 (235 hom., cov: 33)
  • Exomes 𝑓: 0.045 (183 hom.)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+240797A>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6899 AN: 151746 Hom.: 235 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0470

GnomAD4 exome AF: 0.0447 AC: 6342 AN: 141776 Hom.: 183 AF XY: 0.0442 AC XY: 3079 AN XY: 69732

Gnomad4 AFR exome AF: 0.00902

Gnomad4 AMR exome AF: 0.0268

Gnomad4 ASJ exome AF: 0.0165

Gnomad4 EAS exome AF: 0.0476

Gnomad4 SAS exome AF: 0.0361

Gnomad4 FIN exome AF: 0.0503

Gnomad4 NFE exome AF: 0.0489

Gnomad4 OTH exome AF: 0.0426

GnomAD4 genome AF: 0.0454 AC: 6894 AN: 151852 Hom.: 235 Cov.: 33 AF XY: 0.0459 AC XY: 3405 AN XY: 74250

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0548

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0597

Gnomad4 OTH AF: 0.0471

Alfa AF: 0.0550 Hom.: 46

Bravo AF: 0.0408

Asia WGS AF: 0.0850 AC: 295 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28357093; hg19: chr6-43737805;