13-27622067-G-T

Position:

• chr13-27622067-G-T

Variant summary

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

The NM_015972.4(POLR1D):​c.26+58G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,480,350 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (139 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (109 hom.)
• Consequence: POLR1D NM_015972.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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=-0.67).
• BP6: Variant 13-27622067-G-T is Benign according to our data. Variant chr13-27622067-G-T is described in ClinVar as [Benign]. Clinvar id is 1289199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1D	NM_015972.4	c.26+58G>T		intron_variant		ENST00000302979.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1D	ENST00000302979.5	c.26+58G>T		intron_variant		1	NM_015972.4	P1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3381 AN: 152184 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

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: 0.000235

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00234 AC: 3111 AN: 1328048 Hom.: 109 Cov.: 23 AF XY: 0.00198 AC XY: 1306 AN XY: 659134

Gnomad4 AFR exome AF: 0.0828

Gnomad4 AMR exome AF: 0.00439

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000153

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000534

Gnomad4 OTH exome AF: 0.00542

GnomAD4 genome AF: 0.0222 AC: 3382 AN: 152302 Hom.: 139 Cov.: 32 AF XY: 0.0217 AC XY: 1619 AN XY: 74460

Gnomad4 AFR AF: 0.0767

Gnomad4 AMR AF: 0.00901

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0186 Hom.: 12

Bravo AF: 0.0259

Asia WGS AF: 0.00462 AC: 17 AN: 3478

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 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.96
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.0

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: rs2232682; hg19: chr13-28196204;