6-43769958-CAG-C

Position:

• chr6-43769958-CAG-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001318876.2(POLR1C):​c.945+240690_945+240691del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 152,342 control chromosomes in the GnomAD database, including 14 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.010 (14 hom., cov: 32)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0104 (1585/152342) while in subpopulation NFE AF= 0.0172 (1173/68028). AF 95% confidence interval is 0.0164. There are 14 homozygotes in gnomad4. There are 700 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+240690_945+240691del		intron_variant			NP_001305805.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1584 AN: 152224 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00321

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.00382

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

GnomAD4 genome AF: 0.0104 AC: 1585 AN: 152342 Hom.: 14 Cov.: 32 AF XY: 0.00940 AC XY: 700 AN XY: 74502

Gnomad4 AFR AF: 0.00320

Gnomad4 AMR AF: 0.00850

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.0119 Hom.: 0

Bravo AF: 0.0104

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57743727; hg19: chr6-43737695;