6-43751654-G-T

Position:

• chr6-43751654-G-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+222383G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,092 control chromosomes in the GnomAD database, including 8,386 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 0.33 (8386 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2	c.945+222383G>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49938 AN: 151974 Hom.: 8373 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.329 AC: 49996 AN: 152092 Hom.: 8386 Cov.: 33 AF XY: 0.326 AC XY: 24260 AN XY: 74342

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.317

Alfa AF: 0.349 Hom.: 12459

Bravo AF: 0.316

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9394963; hg19: chr6-43719391;