rs34768748

chr5-71532319-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018429.3(BDP1):c.5784T>G(p.Thr1928=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,613,392 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (29 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (21 hom.)
• Consequence: BDP1 NM_018429.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.26

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-71532319-T-G is Benign according to our data. Variant chr5-71532319-T-G is described in ClinVar as [Benign]. Clinvar id is 585479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.26 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0099 (1508/152336) while in subpopulation AFR AF= 0.0341 (1419/41572). AF 95% confidence interval is 0.0327. There are 29 homozygotes in gnomad4. There are 711 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDP1	NM_018429.3	c.5784T>G	p.Thr1928=	synonymous_variant	26/39	ENST00000358731.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDP1	ENST00000358731.9	c.5784T>G	p.Thr1928=	synonymous_variant	26/39	1	NM_018429.3	P1
BDP1	ENST00000508917.6	n.5976T>G		non_coding_transcript_exon_variant	26/32	1
BDP1	ENST00000514903.7	c.555T>G	p.Thr185=	synonymous_variant, NMD_transcript_variant	3/16	5

Frequencies

GnomAD3 genomes AF: 0.00990 AC: 1507 AN: 152218 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00253 AC: 629 AN: 248992 Hom.: 4 AF XY: 0.00182 AC XY: 246 AN XY: 135098

Gnomad AFR exome AF: 0.0342

Gnomad AMR exome AF: 0.00227

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000882 AC: 1288 AN: 1461056 Hom.: 21 Cov.: 30 AF XY: 0.000710 AC XY: 516 AN XY: 726792

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000581

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00990 AC: 1508 AN: 152336 Hom.: 29 Cov.: 32 AF XY: 0.00954 AC XY: 711 AN XY: 74492

Gnomad4 AFR AF: 0.0341

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00513 Hom.: 3

Bravo AF: 0.0110

Asia WGS AF: 0.00202 AC: 7 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	clinical testing	GeneDx	Jul 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.093
Dann	Benign	0.50

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: rs34768748; hg19: chr5-70828146;