13-27622184-A-G

Position:

• chr13-27622184-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015972.4(POLR1D):​c.26+175A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 643,866 control chromosomes in the GnomAD database, including 4,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1599 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3246 hom.)
• Consequence: POLR1D NM_015972.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

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 -10 ACMG points.

• BP6: Variant 13-27622184-A-G is Benign according to our data. Variant chr13-27622184-A-G is described in ClinVar as [Benign]. Clinvar id is 1244891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1D	NM_015972.4	c.26+175A>G		intron_variant		ENST00000302979.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1D	ENST00000302979.5	c.26+175A>G		intron_variant		1	NM_015972.4	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19925 AN: 152094 Hom.: 1597 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.105 AC: 51559 AN: 491650 Hom.: 3246 Cov.: 5 AF XY: 0.105 AC XY: 27404 AN XY: 261884

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.0810

Gnomad4 ASJ exome AF: 0.0944

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0663

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.131 AC: 19954 AN: 152216 Hom.: 1599 Cov.: 32 AF XY: 0.130 AC XY: 9675 AN XY: 74436

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0939

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0402 Hom.: 32

Bravo AF: 0.140

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.064
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: -5

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

Publications

LitVar

Other links and lift over

dbSNP: rs73432869; hg19: chr13-28196321;