rs1570360

Positions:

• chr6-43770093-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001318876.2(POLR1C):​c.945+240822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 291,618 control chromosomes in the GnomAD database, including 79,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44210 hom., cov: 32)
  • Exomes 𝑓: 0.71 (35290 hom.)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.275

Genes affected

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-43770093-A-G is Benign according to our data. Variant chr6-43770093-A-G is described in ClinVar as [Benign]. Clinvar id is 1226235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.945+240822A>G		intron_variant			NP_001305805.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114652 AN: 151704 Hom.: 44151 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.757

GnomAD4 exome AF: 0.706 AC: 98753 AN: 139804 Hom.: 35290 AF XY: 0.703 AC XY: 48389 AN XY: 68808

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.754

Gnomad4 ASJ exome AF: 0.706

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.634

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.756 AC: 114765 AN: 151814 Hom.: 44210 Cov.: 32 AF XY: 0.755 AC XY: 56029 AN XY: 74190

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.758

Alfa AF: 0.693 Hom.: 29333

Bravo AF: 0.774

Asia WGS AF: 0.789 AC: 2734 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

This variant is associated with the following publications: (PMID: 24902660, 23962084, 12067976, 23007030, 11752046, 23404364, 10626738, 21831507) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1570360; hg19: chr6-43737830;