2-86082987-C-T

Variant summary

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

The NM_015425.6(POLR1A):c.817+95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 933,548 control chromosomes in the GnomAD database, including 308,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (42483 hom., cov: 31)
  • Exomes 𝑓: 0.82 (265599 hom.)
• Consequence: POLR1A NM_015425.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

Genes affected

POLR1A (HGNC:17264): (RNA polymerase I subunit A) The protein encoded by this gene is the largest subunit of the RNA polymerase I complex. The encoded protein represents the catalytic subunit of the complex, which transcribes DNA into ribosomal RNA precursors. Defects in this gene are a cause of the Cincinnati type of acrofacial dysostosis. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-86082987-C-T is Benign according to our data. Variant chr2-86082987-C-T is described in ClinVar as [Benign]. Clinvar id is 1287885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1A	NM_015425.6	c.817+95G>A		intron_variant		ENST00000263857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1A	ENST00000263857.11	c.817+95G>A		intron_variant		1	NM_015425.6	P2

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110672 AN: 151870 Hom.: 42475 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.821 AC: 641291 AN: 781560 Hom.: 265599 AF XY: 0.823 AC XY: 335889 AN XY: 408210

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.887

Gnomad4 EAS exome AF: 0.653

Gnomad4 SAS exome AF: 0.820

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.840

Gnomad4 OTH exome AF: 0.810

GnomAD4 genome AF: 0.728 AC: 110723 AN: 151988 Hom.: 42483 Cov.: 31 AF XY: 0.731 AC XY: 54305 AN XY: 74282

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.776

Alfa AF: 0.828 Hom.: 104389

Bravo AF: 0.716

Asia WGS AF: 0.716 AC: 2490 AN: 3478

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

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.14
Dann	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2288118; hg19: chr2-86310110; COSMIC: COSV55697315; COSMIC: COSV55697315;