6-43767412-G-T

Position:

• chr6-43767412-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+238141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,196 control chromosomes in the GnomAD database, including 4,922 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 0.25 (4922 hom., cov: 33)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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 = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+238141G>T		intron_variant			NP_001305805.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38125 AN: 152078 Hom.: 4917 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.251 AC: 38133 AN: 152196 Hom.: 4922 Cov.: 33 AF XY: 0.249 AC XY: 18552 AN XY: 74396

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.274

Alfa AF: 0.235 Hom.: 528

Bravo AF: 0.261

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs833060; hg19: chr6-43735149;