rs12584838

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_152705.3(POLR1D):​c.27-11208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00018 ( 0 hom., cov: 32)

Consequence

POLR1D
NM_152705.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.429
Variant links:
Genes affected
POLR1D (HGNC:20422): (RNA polymerase I and III subunit D) The protein encoded by this gene is a component of the RNA polymerase I and RNA polymerase III complexes, which function in the synthesis of ribosomal RNA precursors and small RNAs, respectively. Mutations in this gene are a cause of Treacher Collins syndrome (TCS), a craniofacial development disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000184 (28/152060) while in subpopulation NFE AF= 0.000397 (27/68000). AF 95% confidence interval is 0.00028. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POLR1DNM_152705.3 linkc.27-11208G>A intron_variant Intron 1 of 2 NP_689918.1 P0DPB5-1
POLR1DNM_001206559.2 linkc.-58-11208G>A intron_variant Intron 1 of 2 NP_001193488.1 P0DPB5A0A087WTY1
POLR1DXM_047430381.1 linkc.27-11208G>A intron_variant Intron 2 of 3 XP_047286337.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POLR1DENST00000399697.7 linkc.27-11208G>A intron_variant Intron 1 of 2 1 ENSP00000382604.3 P0DPB5-1
POLR1DENST00000621089.2 linkc.-58-11208G>A intron_variant Intron 1 of 2 1 ENSP00000478213.1 A0A087WTY1
POLR1DENST00000489647.4 linkc.27-11208G>A intron_variant Intron 1 of 2 1 ENSP00000483656.1 A0A087X0U2

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152060
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152060
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000118
Hom.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.1
DANN
Benign
0.75

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12584838; hg19: chr13-28211308; API