2-112553197-A-T

Variant names:

• chr2-112553197-A-T
• rs9308672
• NM_019014.6:c.1158+381A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019014.6(POLR1B):​c.1158+381A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,188 control chromosomes in the GnomAD database, including 2,095 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 0.15 (2095 hom., cov: 32)
• Consequence: POLR1B NM_019014.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 4 publications found

Genes affected

POLR1B (HGNC:20454): (RNA polymerase I subunit B) Eukaryotic RNA polymerase I (pol I) is responsible for the transcription of ribosomal RNA (rRNA) genes and production of rRNA, the primary component of ribosomes. Pol I is a multisubunit enzyme composed of 6 to 14 polypeptides, depending on the species. Most of the mass of the pol I complex derives from the 2 largest subunits, Rpa1 and Rpa2 in yeast. POLR1B is homologous to Rpa2 (Seither and Grummt, 1996 [PubMed 8921381]).[supplied by OMIM, Mar 2008]

POLR1B Gene-Disease associations (from GenCC):

• Treacher Collins syndrome 4

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• Treacher-Collins syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019014.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1B	NM_019014.6	MANE Select	c.1158+381A>T		intron	N/A	NP_061887.2
	POLR1B	NM_001371969.1		c.1158+381A>T		intron	N/A	NP_001358898.1
	POLR1B	NM_001282772.2		c.1272+381A>T		intron	N/A	NP_001269701.1	Q9H9Y6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1B	ENST00000263331.10	TSL:2 MANE Select	c.1158+381A>T		intron	N/A	ENSP00000263331.5	Q9H9Y6-1
	POLR1B	ENST00000409894.7	TSL:1	c.1158+381A>T		intron	N/A	ENSP00000387143.3	Q9H9Y6-5
	POLR1B	ENST00000333990.10	TSL:1	n.*1028+381A>T		intron	N/A	ENSP00000334589.6	F8WAK7

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22422 AN: 152070 Hom.: 2089 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.148 AC: 22453 AN: 152188 Hom.: 2095 Cov.: 32 AF XY: 0.149 AC XY: 11057 AN XY: 74426

African (AFR) AF: 0.239 AC: 9928 AN: 41500

American (AMR) AF: 0.182 AC: 2789 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1651 AN: 5172

South Asian (SAS) AF: 0.143 AC: 692 AN: 4834

European-Finnish (FIN) AF: 0.0852 AC: 903 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5693 AN: 68012

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.0449 Hom.: 35

Bravo AF: 0.163

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.70
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9308672; hg19: chr2-113310774;