Variant chr13-27621835-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000399697.7(POLR1D):c.-149C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 788,718 control chromosomes in the GnomAD database, including 5,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 825 hom., cov: 33)

Exomes 𝑓: 0.11 ( 4349 hom. )

Consequence

POLR1D
ENST00000399697.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.344

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]

POLR1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 13-27621835-C-T is Benign according to our data. Variant chr13-27621835-C-T is described in ClinVar as [Benign]. Clinvar id is 1238128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
POLR1D	NM_001374407.1 linkuse as main transcript	c.-149C>T	5_prime_UTR_variant	2/3
POLR1D	XM_047430381.1 linkuse as main transcript	c.-149C>T	5_prime_UTR_variant	2/4
POLR1D	NM_001206559.2 linkuse as main transcript	c.-59+695C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	UniProt
POLR1D	ENST00000399697.7 linkuse as main transcript	c.-149C>T	5_prime_UTR_variant	1/3	1	P0DPB5-1
POLR1D	ENST00000621089.2 linkuse as main transcript	c.-59+695C>T	intron_variant		1
POLR1D	ENST00000627604.1 linkuse as main transcript	c.-59+398C>T	intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15388

AN:

152028

Hom.:

824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0847

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.0708

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0180

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0946

GnomAD4 exome

AF:

0.111

AC:

70829

AN:

636576

Hom.:

4349

Cov.:

AF XY:

0.112

AC XY:

37639

AN XY:

334810

show subpopulations

Gnomad4 AFR exome

AF:

0.0860

Gnomad4 AMR exome

AF:

0.0530

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.0140

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.101

AC:

15385

AN:

152142

Hom.:

825

Cov.:

AF XY:

0.102

AC XY:

7561

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0846

Gnomad4 AMR

AF:

0.0707

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0181

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.0941

Alfa

AF:

0.0561

Hom.:

Bravo

AF:

0.0926

Asia WGS

AF:

0.0760

AC:

266

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.95

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over