13-27622698-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015972.4(POLR1D):c.27-177A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 594,968 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: POLR1D NM_015972.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.00

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=-0.81).
• BP6: Variant 13-27622698-A-T is Benign according to our data. Variant chr13-27622698-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1211448.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00539 (821/152312) while in subpopulation AFR AF= 0.0172 (713/41562). AF 95% confidence interval is 0.0161. There are 5 homozygotes in gnomad4. There are 379 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1D	NM_015972.4	c.27-177A>T		intron_variant		ENST00000302979.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1D	ENST00000302979.5	c.27-177A>T		intron_variant		1	NM_015972.4	P1

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 811 AN: 152194 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00102 AC: 452 AN: 442656 Hom.: 0 AF XY: 0.000959 AC XY: 224 AN XY: 233652

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.00319

Gnomad4 ASJ exome AF: 0.0000745

Gnomad4 EAS exome AF: 0.0000334

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.0000296

Gnomad4 NFE exome AF: 0.000392

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.00539 AC: 821 AN: 152312 Hom.: 5 Cov.: 32 AF XY: 0.00509 AC XY: 379 AN XY: 74502

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00423 Hom.: 1

Bravo AF: 0.00661

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.39
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: rs113105826; hg19: chr13-28196835;