chr22-38003091-A-G

Variant names:

• chr22-38003091-A-G
• rs139897
• NM_001301130.2:c.452+16779A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POLR2F	NM_001301130.2	c.452+16779A>G		intron_variant	Intron 5 of 5		NP_001288059.1
POLR2F	NM_001363825.1	c.*38+30781A>G		intron_variant	Intron 5 of 5		NP_001350754.1
POLR2F	NM_001301131.2	c.293+35921A>G		intron_variant	Intron 4 of 4		NP_001288060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR2F	ENST00000407936.5	c.452+16779A>G		intron_variant	Intron 5 of 5	3		ENSP00000385725.1
POLR2F	ENST00000333418.4	c.119+16779A>G		intron_variant	Intron 1 of 2	2		ENSP00000332130.4
POLR2F	ENST00000405557.5	c.294-22488A>G		intron_variant	Intron 4 of 4	5		ENSP00000384112.1
POLR2F	ENST00000427034.1	c.112+16779A>G		intron_variant	Intron 1 of 1	2		ENSP00000389307.1

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

African (AFR) AF: 0.826 AC: 34240 AN: 41448

American (AMR) AF: 0.641 AC: 9759 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2072 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3868 AN: 5174

South Asian (SAS) AF: 0.617 AC: 2974 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6476 AN: 10546

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42415 AN: 67958

Other (OTH) AF: 0.652 AC: 1378 AN: 2112

Alfa AF: 0.638 Hom.: 33419

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
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs139897; hg19: chr22-38399098;