chr13-27621752-G-A

Position:

• chr13-27621752-G-A

Variant summary

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

The ENST00000621089.2(POLR1D):​c.-59+612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 354,282 control chromosomes in the GnomAD database, including 664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (189 hom., cov: 32)
  • Exomes 𝑓: 0.063 (475 hom.)
• Consequence: POLR1D ENST00000621089.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.528

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=-0.79).
• BP6: Variant 13-27621752-G-A is Benign according to our data. Variant chr13-27621752-G-A is described in ClinVar as [Benign]. Clinvar id is 1283811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1D	NM_001374407.1	c.-232G>A		5_prime_UTR_variant	2/3
POLR1D	XM_047430381.1	c.-232G>A		5_prime_UTR_variant	2/4
POLR1D	NM_001206559.2	c.-59+612G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1D	ENST00000621089.2	c.-59+612G>A		intron_variant		1
POLR1D	ENST00000627604.1	c.-59+315G>A		intron_variant		4
POLR1D	ENST00000637180.1	c.-59+315G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6414 AN: 151790 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.00938

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0258

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0478

GnomAD4 exome AF: 0.0632 AC: 12782 AN: 202384 Hom.: 475 Cov.: 3 AF XY: 0.0643 AC XY: 6720 AN XY: 104538

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0360

Gnomad4 FIN exome AF: 0.0673

Gnomad4 NFE exome AF: 0.0739

Gnomad4 OTH exome AF: 0.0538

GnomAD4 genome AF: 0.0422 AC: 6414 AN: 151898 Hom.: 189 Cov.: 32 AF XY: 0.0407 AC XY: 3025 AN XY: 74250

Gnomad4 AFR AF: 0.00935

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0584

Gnomad4 NFE AF: 0.0641

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0589 Hom.: 37

Bravo AF: 0.0383

Asia WGS AF: 0.0110 AC: 37 AN: 3452

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.56
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs2232675; hg19: chr13-28195889;