rs1961760

Positions:

• chr5-71510822-T-A
• chr5-71510822-T-G

Variant summary

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

The ENST00000358731.9(BDP1):​c.3730T>A​(p.Phe1244Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,612,654 control chromosomes in the GnomAD database, including 187,022 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15694 hom., cov: 33)
  • Exomes 𝑓: 0.48 (171328 hom.)
• Consequence: BDP1 ENST00000358731.9 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0710

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.523905E-5).
• BP6: Variant 5-71510822-T-A is Benign according to our data. Variant chr5-71510822-T-A is described in ClinVar as [Benign]. Clinvar id is 508086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDP1	NM_018429.3	c.3730T>A	p.Phe1244Ile	missense_variant	17/39	ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.3730T>A	p.Phe1244Ile	missense_variant	17/39	1	NM_018429.3	ENSP00000351575	P1
BDP1	ENST00000508917.6	n.3922T>A		non_coding_transcript_exon_variant	17/32	1
BDP1	ENST00000508157.3	n.2875T>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68252 AN: 151732 Hom.: 15685 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.450

GnomAD3 exomes AF: 0.457 AC: 113372 AN: 248262 Hom.: 26938 AF XY: 0.468 AC XY: 63119 AN XY: 134814

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.374

Gnomad SAS exome AF: 0.556

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.485

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.481 AC: 703328 AN: 1460806 Hom.: 171328 Cov.: 52 AF XY: 0.485 AC XY: 352182 AN XY: 726802

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.484

Gnomad4 EAS exome AF: 0.372

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.450 AC: 68291 AN: 151848 Hom.: 15694 Cov.: 33 AF XY: 0.452 AC XY: 33519 AN XY: 74228

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.449

Alfa AF: 0.475 Hom.: 13031

Bravo AF: 0.428

TwinsUK AF: 0.474 AC: 1756

ALSPAC AF: 0.501 AC: 1932

ESP6500AA AF: 0.387 AC: 1415

ESP6500EA AF: 0.483 AC: 3943

ExAC AF: 0.463 AC: 55890

Asia WGS AF: 0.450 AC: 1566 AN: 3478

EpiCase AF: 0.479

EpiControl AF: 0.477

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 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. -

Hearing loss, autosomal recessive 112 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.039
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
DANN	Benign	0.19
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.091	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.9	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.93	N
REVEL	Benign	0.0040
Sift	Benign	1.0	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.037
MPC		0.046
ClinPred		0.00016	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.020

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: rs1961760; hg19: chr5-70806649; COSMIC: COSV62430362; COSMIC: COSV62430362;