Genetic Variant POLR1D:c.*49C>T (chr13-27623299-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_015972.4(POLR1D):c.*49C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,609,720 control chromosomes in the GnomAD database, including 124,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9240 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114871 hom. )

Consequence

POLR1D
NM_015972.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.428

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=-0.86).

BP6

Variant 13-27623299-C-T is Benign according to our data. Variant chr13-27623299-C-T is described in ClinVar as [Benign]. Clinvar id is 1258656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-27623299-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1D	NM_015972.4 link	c.*49C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000302979.5	NP_057056.1	P0DPB6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1D	ENST00000302979.5 link	c.*49C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_015972.4	ENSP00000302478.4		P0DPB6-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48092

AN:

151934

Hom.:

9231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0979

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.316

GnomAD3 exomes

AF:

0.405

AC:

98061

AN:

241828

Hom.:

21326

AF XY:

0.399

AC XY:

52748

AN XY:

132210

show subpopulations

Gnomad AFR exome

AF:

0.0959

Gnomad AMR exome

AF:

0.577

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.471

Gnomad SAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.391

AC:

570366

AN:

1457668

Hom.:

114871

Cov.:

AF XY:

0.391

AC XY:

283347

AN XY:

725138

show subpopulations

Gnomad4 AFR exome

AF:

0.0882

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.521

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.316

AC:

48112

AN:

152052

Hom.:

9240

Cov.:

AF XY:

0.321

AC XY:

23828

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0977

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.392

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.317

Alfa

AF:

0.380

Hom.:

25896

Bravo

AF:

0.314

Asia WGS

AF:

0.417

AC:

1448

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.14

DANN

Benign

0.69

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