rs139897

Positions:

• chr22-38003091-A-G
• chr22-38003091-A-T

Variant summary

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

The NM_001301130.2(POLR2F):​c.452+16779A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 151,956 control chromosomes in the GnomAD database, including 36,209 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 0.68 (36209 hom., cov: 30)
• Consequence: POLR2F NM_001301130.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

Genes affected

POLR2F (HGNC:9193): (RNA polymerase II, I and III subunit F) This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2F	NM_001301130.2	c.452+16779A>G		intron_variant			NP_001288059.1
POLR2F	NM_001301131.2	c.293+35921A>G		intron_variant			NP_001288060.1
POLR2F	NM_001363825.1	c.*38+30781A>G		intron_variant			NP_001350754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR2F	ENST00000333418.4	c.120+16779A>G		intron_variant		2		ENSP00000332130
POLR2F	ENST00000405557.5	c.294-22488A>G		intron_variant		5		ENSP00000384112
POLR2F	ENST00000407936.5	c.452+16779A>G		intron_variant		3		ENSP00000385725
POLR2F	ENST00000427034.1	c.114+16779A>G		intron_variant		2		ENSP00000389307

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103766 AN: 151838 Hom.: 36166 Cov.: 30

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.684 AC: 103876 AN: 151956 Hom.: 36209 Cov.: 30 AF XY: 0.680 AC XY: 50510 AN XY: 74240

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.652

Alfa AF: 0.637 Hom.: 21207

Bravo AF: 0.692

Asia WGS AF: 0.683 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.4
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: rs139897; hg19: chr22-38399098;