rs535534

Positions:

• chr13-27635186-A-G

Variant summary

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

The ENST00000399697.7(POLR1D):​c.26+13177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,010 control chromosomes in the GnomAD database, including 21,034 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 0.49 (21034 hom., cov: 31)
• Consequence: POLR1D ENST00000399697.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1D	NM_001206559.2	c.-58-13193A>G		intron_variant			NP_001193488.1
POLR1D	NM_152705.3	c.26+13177A>G		intron_variant			NP_689918.1
POLR1D	XM_047430381.1	c.26+13177A>G		intron_variant			XP_047286337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1D	ENST00000399697.7	c.26+13177A>G		intron_variant		1		ENSP00000382604
POLR1D	ENST00000489647.4	c.26+13177A>G		intron_variant		1		ENSP00000483656
POLR1D	ENST00000621089.2	c.-58-13193A>G		intron_variant		1		ENSP00000478213

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75097 AN: 151890 Hom.: 21020 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.494 AC: 75127 AN: 152010 Hom.: 21034 Cov.: 31 AF XY: 0.499 AC XY: 37080 AN XY: 74282

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.534

Alfa AF: 0.556 Hom.: 12796

Bravo AF: 0.489

Asia WGS AF: 0.624 AC: 2171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs535534; hg19: chr13-28209323; COSMIC: COSV68800057;