rs503699

Positions:

• chr13-27640597-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152705.3(POLR1D):​c.27-7782G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,000 control chromosomes in the GnomAD database, including 7,791 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 0.29 (7791 hom., cov: 32)
• Consequence: POLR1D NM_152705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1D	NM_152705.3	c.27-7782G>C		intron_variant			NP_689918.1
POLR1D	NM_001206559.2	c.-58-7782G>C		intron_variant			NP_001193488.1
POLR1D	XM_047430381.1	c.27-7782G>C		intron_variant			XP_047286337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1D	ENST00000399697.7	c.27-7782G>C		intron_variant		1		ENSP00000382604.3
POLR1D	ENST00000621089.2	c.-58-7782G>C		intron_variant		1		ENSP00000478213.1
POLR1D	ENST00000489647.4	c.27-7782G>C		intron_variant		1		ENSP00000483656.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43957 AN: 151882 Hom.: 7783 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.289 AC: 43979 AN: 152000 Hom.: 7791 Cov.: 32 AF XY: 0.292 AC XY: 21715 AN XY: 74262

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.305

Alfa AF: 0.324 Hom.: 1156

Bravo AF: 0.281

Asia WGS AF: 0.296 AC: 1030 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs503699; hg19: chr13-28214734;