rs35131626

chr5-71539065-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_018429.3(BDP1):c.5916C>A(p.Ile1972=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,599,206 control chromosomes in the GnomAD database, including 791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (73 hom., cov: 32)
  • Exomes 𝑓: 0.027 (718 hom.)
• Consequence: BDP1 NM_018429.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.250

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 5-71539065-C-A is Benign according to our data. Variant chr5-71539065-C-A is described in ClinVar as [Benign]. Clinvar id is 508602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDP1	NM_018429.3	c.5916C>A	p.Ile1972=	synonymous_variant	27/39	ENST00000358731.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDP1	ENST00000358731.9	c.5916C>A	p.Ile1972=	synonymous_variant	27/39	1	NM_018429.3	P1
BDP1	ENST00000508917.6	n.6108C>A		non_coding_transcript_exon_variant	27/32	1
BDP1	ENST00000525844.1	c.78C>A	p.Ile26=	synonymous_variant, NMD_transcript_variant	2/14	1
BDP1	ENST00000514903.7	c.687C>A	p.Ile229=	synonymous_variant, NMD_transcript_variant	4/16	5

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3804 AN: 152030 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0235

GnomAD3 exomes AF: 0.0321 AC: 7825 AN: 244140 Hom.: 192 AF XY: 0.0336 AC XY: 4452 AN XY: 132604

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.0369

Gnomad ASJ exome AF: 0.0241

Gnomad EAS exome AF: 0.0114

Gnomad SAS exome AF: 0.0640

Gnomad FIN exome AF: 0.0353

Gnomad NFE exome AF: 0.0288

Gnomad OTH exome AF: 0.0266

GnomAD4 exome AF: 0.0274 AC: 39620 AN: 1447058 Hom.: 718 Cov.: 28 AF XY: 0.0286 AC XY: 20637 AN XY: 720324

Gnomad4 AFR exome AF: 0.00870

Gnomad4 AMR exome AF: 0.0366

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.00814

Gnomad4 SAS exome AF: 0.0650

Gnomad4 FIN exome AF: 0.0360

Gnomad4 NFE exome AF: 0.0251

Gnomad4 OTH exome AF: 0.0256

GnomAD4 genome AF: 0.0250 AC: 3805 AN: 152148 Hom.: 73 Cov.: 32 AF XY: 0.0257 AC XY: 1909 AN XY: 74364

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.0735

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0257 Hom.: 32

Bravo AF: 0.0220

Asia WGS AF: 0.0410 AC: 141 AN: 3476

EpiCase AF: 0.0246

EpiControl AF: 0.0238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 28, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	7.0
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35131626; hg19: chr5-70834892;