2-86103603-A-G

Position:

• chr2-86103603-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015425.6(POLR1A):​c.77+2097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,230 control chromosomes in the GnomAD database, including 58,900 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 0.88 (58900 hom., cov: 33)
• Consequence: POLR1A NM_015425.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1A	NM_015425.6	c.77+2097T>C		intron_variant		ENST00000263857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1A	ENST00000263857.11	c.77+2097T>C		intron_variant		1	NM_015425.6	P2

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133384 AN: 152110 Hom.: 58867 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.877 AC: 133475 AN: 152230 Hom.: 58900 Cov.: 33 AF XY: 0.878 AC XY: 65372 AN XY: 74432

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.903

Alfa AF: 0.914 Hom.: 128788

Bravo AF: 0.873

Asia WGS AF: 0.926 AC: 3221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.52
DANN	Benign	0.72

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: rs10779967; hg19: chr2-86330726;