12-106358027-G-A

Position:

• chr12-106358027-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018082.6(POLR3B):​c.72+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,578,502 control chromosomes in the GnomAD database, including 41,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5187 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35813 hom.)
• Consequence: POLR3B NM_018082.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.252

Genes affected

POLR3B (HGNC:30348): (RNA polymerase III subunit B) This gene encodes the second largest subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The largest subunit and the encoded protein form the catalytic center of RNA polymerase III. Mutations in this gene are a cause of hypomyelinating leukodystrophy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-106358027-G-A is Benign according to our data. Variant chr12-106358027-G-A is described in ClinVar as [Benign]. Clinvar id is 1296582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR3B	NM_018082.6	c.72+76G>A		intron_variant		ENST00000228347.9	NP_060552.4
POLR3B	XM_017019621.3	c.72+76G>A		intron_variant			XP_016875110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR3B	ENST00000228347.9	c.72+76G>A		intron_variant		1	NM_018082.6	ENSP00000228347.4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37607 AN: 152034 Hom.: 5178 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.220 AC: 313526 AN: 1426350 Hom.: 35813 Cov.: 33 AF XY: 0.219 AC XY: 155299 AN XY: 707642

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.0555

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.247 AC: 37647 AN: 152152 Hom.: 5187 Cov.: 33 AF XY: 0.243 AC XY: 18088 AN XY: 74402

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0545

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.220

Alfa AF: 0.121 Hom.: 188

Bravo AF: 0.254

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.59
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs61943670; hg19: chr12-106751805; COSMIC: COSV57278150; COSMIC: COSV57278150;