rs279290

Positions:

• chr5-71544606-A-G

Variant summary

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

The NM_018429.3(BDP1):​c.6563+99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,329,880 control chromosomes in the GnomAD database, including 156,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16664 hom., cov: 32)
  • Exomes 𝑓: 0.49 (139597 hom.)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.32

Genes affected

BDP1 (HGNC:13652): (B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB) The product of this gene is a subunit of the TFIIIB transcription initiation complex, which recruits RNA polymerase III to target promoters in order to initiate transcription. The encoded protein localizes to concentrated aggregates in the nucleus, and is required for transcription from all three types of polymerase III promoters. It is phosphorylated by casein kinase II during mitosis, resulting in its release from chromatin and suppression of polymerase III transcription. [provided by RefSeq, Jul 2008]

BDP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 5-71544606-A-G is Benign according to our data. Variant chr5-71544606-A-G is described in ClinVar as [Benign]. Clinvar id is 1228769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDP1	NM_018429.3	c.6563+99A>G		intron_variant		ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.6563+99A>G		intron_variant		1	NM_018429.3	ENSP00000351575.4
BDP1	ENST00000508917.6	n.6755+99A>G		intron_variant		1
BDP1	ENST00000525844.1	n.629+99A>G		intron_variant		1		ENSP00000432404.1
BDP1	ENST00000514903.7	n.1328+99A>G		intron_variant		5		ENSP00000421910.3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70509 AN: 151846 Hom.: 16654 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.487 AC: 573893 AN: 1177916 Hom.: 139597 AF XY: 0.489 AC XY: 287142 AN XY: 587170

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.487

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.464 AC: 70554 AN: 151964 Hom.: 16664 Cov.: 32 AF XY: 0.465 AC XY: 34564 AN XY: 74252

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.458

Alfa AF: 0.467 Hom.: 2075

Bravo AF: 0.445

Asia WGS AF: 0.452 AC: 1572 AN: 3478

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	Jun 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs279290; hg19: chr5-70840433;