rs606231341

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 156719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR2F	NM_001301130.2	c.453-24294G>C		intron_variant	Intron 5 of 5		NP_001288059.1
POLR2F	NM_001363825.1	c.*39-24294G>C		intron_variant	Intron 5 of 5		NP_001350754.1
POLR2F	NM_001301131.2	c.294-24294G>C		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.453-24294G>C		intron_variant	Intron 5 of 5	3		ENSP00000385725.1
POLR2F	ENST00000333418.4	c.120-9095G>C		intron_variant	Intron 1 of 2	2		ENSP00000332130.4
POLR2F	ENST00000405557.5	c.294-8805G>C		intron_variant	Intron 4 of 4	5		ENSP00000384112.1
POLR2F	ENST00000427034.1	c.113-9095G>C		intron_variant	Intron 1 of 1	2		ENSP00000389307.1

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

Gnomad4 AFR AF: 0.000290

Gnomad4 AMR AF: 0.000459

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000286

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.000952

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Hirschsprung disease, susceptibility to, 1 Pathogenic:1

Dec 11, 2013

U955 Equipe 11, INSERM

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: in vitro

Regulation of SOX10 expression -

SOX10-related disorder Benign:1

May 16, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SOX10: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs533778281; hg19: chr22-38412781;