13-27621896-G-C

Position:

• chr13-27621896-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015972.4(POLR1D):​c.-88G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,418,632 control chromosomes in the GnomAD database, including 10,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1365 hom., cov: 33)
  • Exomes 𝑓: 0.12 (8710 hom.)
• Consequence: POLR1D NM_015972.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.208

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 13-27621896-G-C is Benign according to our data. Variant chr13-27621896-G-C is described in ClinVar as [Benign]. Clinvar id is 1244100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1D	NM_015972.4	c.-88G>C		5_prime_UTR_variant	1/2	ENST00000302979.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1D	ENST00000302979.5	c.-88G>C		5_prime_UTR_variant	1/2	1	NM_015972.4	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19613 AN: 152152 Hom.: 1363 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.115 AC: 146064 AN: 1266366 Hom.: 8710 Cov.: 19 AF XY: 0.115 AC XY: 72335 AN XY: 631698

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.0886

Gnomad4 SAS exome AF: 0.0752

Gnomad4 FIN exome AF: 0.0910

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.129 AC: 19636 AN: 152266 Hom.: 1365 Cov.: 33 AF XY: 0.127 AC XY: 9455 AN XY: 74440

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.140

Alfa AF: 0.128 Hom.: 149

Bravo AF: 0.134

Asia WGS AF: 0.105 AC: 367 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2232679; hg19: chr13-28196033;