rs606231341

Variant names:

• chr22-38016774-G-C
• rs533778281
• NM_001301130.2:c.453-24294G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001301130.2(POLR2F):​c.453-24294G>C variant causes a intron change. The variant allele was found at a frequency of 0.000962 in 151,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.00096 (0 hom., cov: 32)
• Consequence: POLR2F NM_001301130.2 intron
• Clinical Significance: Benign criteria provided, single submitter P:1 B:2
• Conservation: PhyloP100: 6.09
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 22-38016774-G-C is Benign according to our data. Variant chr22-38016774-G-C is described in ClinVar as Benign. ClinVar VariationId is 156719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 146 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301130.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2F	NM_001301130.2		c.453-24294G>C		intron	N/A	NP_001288059.1
	POLR2F	NM_001363825.1		c.*39-24294G>C		intron	N/A	NP_001350754.1
	POLR2F	NM_001301131.2		c.294-24294G>C		intron	N/A	NP_001288060.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2F	ENST00000407936.5	TSL:3	c.453-24294G>C		intron	N/A	ENSP00000385725.1
	POLR2F	ENST00000333418.4	TSL:2	c.120-9095G>C		intron	N/A	ENSP00000332130.4
	POLR2F	ENST00000405557.5	TSL:5	c.294-8805G>C		intron	N/A	ENSP00000384112.1

Frequencies

GnomAD3 genomes AF: 0.000962 AC: 146 AN: 151696 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000460

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.00240

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

GnomAD4 genome AF: 0.000962 AC: 146 AN: 151812 Hom.: 0 Cov.: 32 AF XY: 0.000822 AC XY: 61 AN XY: 74176

African (AFR) AF: 0.000290 AC: 12 AN: 41380

American (AMR) AF: 0.000459 AC: 7 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.000286 AC: 3 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00168 AC: 114 AN: 67924

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.000952

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Hirschsprung disease, susceptibility to, 1 (1)
-	-	1	not provided (1)
-	-	1	SOX10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.90
PhyloP100		6.1
Mutation Taster		=32/68	disease causing

Splicing

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

Other links and lift over

dbSNP: rs533778281; hg19: chr22-38412781;