13-27621877-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.-107C>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 0.0036 in 1,220,572 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (74 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (52 hom.)
• Consequence: POLR1D ENST00000399697.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05

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=-0.73).
• BP6: Variant 13-27621877-C-T is Benign according to our data. Variant chr13-27621877-C-T is described in ClinVar as [Benign]. Clinvar id is 1289980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 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: 0.0160 AC: 2436 AN: 152184 Hom.: 73 Cov.: 33

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.00182 AC: 1944 AN: 1068276 Hom.: 52 Cov.: 14 AF XY: 0.00153 AC XY: 825 AN XY: 540512

Gnomad4 AFR exome AF: 0.0570

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.0000438

Gnomad4 EAS exome AF: 0.0000293

Gnomad4 SAS exome AF: 0.000138

Gnomad4 FIN exome AF: 0.0000415

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.00415

GnomAD4 genome AF: 0.0161 AC: 2446 AN: 152296 Hom.: 74 Cov.: 33 AF XY: 0.0165 AC XY: 1225 AN XY: 74458

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.00283 Hom.: 2

Bravo AF: 0.0177

Asia WGS AF: 0.00318 AC: 11 AN: 3476

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

Apr 04, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	15
Dann	Benign	0.94

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: rs2232678; hg19: chr13-28196014;