13-27661759-G-A

Variant names:

• chr13-27661759-G-A
• rs571786
• ENST00000399697.7:c.102-3927G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152705.3(POLR1D):​c.102-3927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,138 control chromosomes in the GnomAD database, including 7,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7983 hom., cov: 32)
• Consequence: POLR1D NM_152705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 5 publications found

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]

POLR1D Gene-Disease associations (from GenCC):

• Treacher Collins syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

  Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152705.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1D	NM_152705.3		c.102-3927G>A		intron	N/A	NP_689918.1
	POLR1D	NM_001206559.2		c.18-3927G>A		intron	N/A	NP_001193488.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1D	ENST00000399697.7	TSL:1	c.102-3927G>A		intron	N/A	ENSP00000382604.3
	POLR1D	ENST00000621089.2	TSL:1	c.18-3927G>A		intron	N/A	ENSP00000478213.1
	POLR1D	ENST00000692944.1		c.27-3927G>A		intron	N/A	ENSP00000510286.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45409 AN: 152020 Hom.: 7976 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45430 AN: 152138 Hom.: 7983 Cov.: 32 AF XY: 0.301 AC XY: 22424 AN XY: 74378

African (AFR) AF: 0.110 AC: 4553 AN: 41542

American (AMR) AF: 0.427 AC: 6519 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3468

East Asian (EAS) AF: 0.244 AC: 1266 AN: 5178

South Asian (SAS) AF: 0.320 AC: 1543 AN: 4816

European-Finnish (FIN) AF: 0.430 AC: 4534 AN: 10556

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24757 AN: 67980

Other (OTH) AF: 0.312 AC: 658 AN: 2110

Alfa AF: 0.317 Hom.: 5733

Bravo AF: 0.292

Asia WGS AF: 0.308 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.77
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs571786; hg19: chr13-28235896;