rs3851634

chr12-106419124-T-C

Variant summary

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

The NM_018082.6(POLR3B):c.1102-8073T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,122 control chromosomes in the GnomAD database, including 4,373 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 0.22 (4373 hom., cov: 32)
• Consequence: POLR3B NM_018082.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR3B	NM_018082.6	c.1102-8073T>C		intron_variant		ENST00000228347.9
POLR3B	NM_001160708.2	c.928-8073T>C		intron_variant
POLR3B	XM_017019621.3	c.1102-8073T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR3B	ENST00000228347.9	c.1102-8073T>C		intron_variant		1	NM_018082.6	P1
POLR3B	ENST00000539066.5	c.928-8073T>C		intron_variant		2
POLR3B	ENST00000549569.1	c.376-8073T>C		intron_variant		4
POLR3B	ENST00000549195.1	n.512-8073T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33541 AN: 152004 Hom.: 4372 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.221 AC: 33545 AN: 152122 Hom.: 4373 Cov.: 32 AF XY: 0.218 AC XY: 16233 AN XY: 74346

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.226

Alfa AF: 0.272 Hom.: 2760

Bravo AF: 0.209

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	14
Dann	Benign	0.81

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: rs3851634; hg19: chr12-106812902;