rs4714772

Positions:

• chr6-44239380-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.946-202510A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,390 control chromosomes in the GnomAD database, including 2,322 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 0.15 (2322 hom., cov: 31)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.946-202510A>C		intron_variant			NP_001305805.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23197 AN: 151272 Hom.: 2322 Cov.: 31

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.153 AC: 23195 AN: 151390 Hom.: 2322 Cov.: 31 AF XY: 0.158 AC XY: 11652 AN XY: 73904

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.151

Alfa AF: 0.166 Hom.: 2269

Bravo AF: 0.154

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.095
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4714772; hg19: chr6-44207117;