13-27621835-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.344

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 -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15388 AN: 152028 Hom.: 824 Cov.: 33

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.: 9 AF XY: 0.112 AC XY: 37639 AN XY: 334810

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.: 33 AF XY: 0.102 AC XY: 7561 AN XY: 74380

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.: 64

Bravo AF: 0.0926

Asia WGS AF: 0.0760 AC: 266 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	17
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

Other links and lift over

dbSNP: rs2232676; hg19: chr13-28195972; COSMIC: COSV57256073; COSMIC: COSV57256073;