rs571786

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-27661759-G-A
• chr13-27661759-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.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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1D	NM_152705.3	c.102-3927G>A		intron_variant	Intron 2 of 2		NP_689918.1
POLR1D	NM_001206559.2	c.18-3927G>A		intron_variant	Intron 2 of 2		NP_001193488.1
POLR1D	XM_017020622.2	c.111-3927G>A		intron_variant	Intron 1 of 1		XP_016876111.1
POLR1D	XM_047430381.1	c.102-3927G>A		intron_variant	Intron 3 of 3		XP_047286337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1D	ENST00000399697.7	c.102-3927G>A		intron_variant	Intron 2 of 2	1		ENSP00000382604.3
POLR1D	ENST00000621089.2	c.18-3927G>A		intron_variant	Intron 2 of 2	1		ENSP00000478213.1
POLR1D	ENST00000692944.1	c.27-3927G>A		intron_variant	Intron 1 of 1			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

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.312

Alfa AF: 0.316 Hom.: 3885

Bravo AF: 0.292

Asia WGS AF: 0.308 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs571786; hg19: chr13-28235896;