13-27622261-G-A

Position:

• chr13-27622261-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015972.4(POLR1D):​c.26+252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 585,468 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (193 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (42 hom.)
• Consequence: POLR1D NM_015972.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-27622261-G-A is Benign according to our data. Variant chr13-27622261-G-A is described in ClinVar as [Benign]. Clinvar id is 1237916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1D	NM_015972.4	c.26+252G>A		intron_variant		ENST00000302979.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1D	ENST00000302979.5	c.26+252G>A		intron_variant		1	NM_015972.4	P1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3806 AN: 152210 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.00304 AC: 1316 AN: 433140 Hom.: 42 Cov.: 0 AF XY: 0.00245 AC XY: 561 AN XY: 229000

Gnomad4 AFR exome AF: 0.0814

Gnomad4 AMR exome AF: 0.00597

Gnomad4 ASJ exome AF: 0.0000764

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000112

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000338

Gnomad4 OTH exome AF: 0.00582

GnomAD4 genome AF: 0.0251 AC: 3820 AN: 152328 Hom.: 193 Cov.: 32 AF XY: 0.0253 AC XY: 1883 AN XY: 74510

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0193 Hom.: 10

Bravo AF: 0.0275

Asia WGS AF: 0.00520 AC: 18 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

Jan 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.35
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs114366700; hg19: chr13-28196398;