13-27621874-C-A

Position:

• chr13-27621874-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000399697.7(POLR1D):​c.-110C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 1,163,736 control chromosomes in the GnomAD database, including 2,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (315 hom., cov: 33)
  • Exomes 𝑓: 0.068 (2588 hom.)
• Consequence: POLR1D ENST00000399697.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 13-27621874-C-A is Benign according to our data. Variant chr13-27621874-C-A is described in ClinVar as [Benign]. Clinvar id is 1246047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1D	NM_015972.4			upstream_gene_variant		ENST00000302979.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1D	ENST00000302979.5			upstream_gene_variant		1	NM_015972.4	P1

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9532 AN: 152138 Hom.: 315 Cov.: 33

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.0535

GnomAD4 exome AF: 0.0676 AC: 68331 AN: 1011486 Hom.: 2588 Cov.: 13 AF XY: 0.0685 AC XY: 35218 AN XY: 514378

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.0311

Gnomad4 ASJ exome AF: 0.0876

Gnomad4 EAS exome AF: 0.0143

Gnomad4 SAS exome AF: 0.0834

Gnomad4 FIN exome AF: 0.0801

Gnomad4 NFE exome AF: 0.0697

Gnomad4 OTH exome AF: 0.0631

GnomAD4 genome AF: 0.0626 AC: 9532 AN: 152250 Hom.: 315 Cov.: 33 AF XY: 0.0634 AC XY: 4716 AN XY: 74436

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.0890

Gnomad4 EAS AF: 0.0180

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0683

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0362 Hom.: 30

Bravo AF: 0.0586

Asia WGS AF: 0.0580 AC: 202 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2232677; hg19: chr13-28196011; COSMIC: COSV57256079; COSMIC: COSV57256079;