rs1961760

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018429.3(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. 15/21 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
NM_018429.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0710

Publications

30 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive 112
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

BDP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018429.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	NM_018429.3	MANE Select	c.3730T>A	p.Phe1244Ile	missense	Exon 17 of 39	NP_060899.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BDP1	ENST00000358731.9	TSL:1 MANE Select	c.3730T>A	p.Phe1244Ile	missense	Exon 17 of 39	ENSP00000351575.4
BDP1	ENST00000508917.6	TSL:1	n.3922T>A		non_coding_transcript_exon	Exon 17 of 32
BDP1	ENST00000508157.3	TSL:5	n.2875T>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68252

AN:

151732

Hom.:

15685

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.457

AC:

113372

AN:

248262

AF XY:

0.468

show subpopulations

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 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.:

AF XY:

0.485

AC XY:

352182

AN XY:

726802

show subpopulations

African (AFR)

AF:

0.393

AC:

13114

AN:

33354

American (AMR)

AF:

0.295

AC:

13125

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

12646

AN:

26110

East Asian (EAS)

AF:

0.372

AC:

14780

AN:

39696

South Asian (SAS)

AF:

0.551

AC:

47461

AN:

86140

European-Finnish (FIN)

AF:

0.528

AC:

28172

AN:

53398

Middle Eastern (MID)

AF:

0.493

AC:

2842

AN:

5764

European-Non Finnish (NFE)

AF:

0.488

AC:

542367

AN:

1111492

Other (OTH)

AF:

0.478

AC:

28821

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20770

41540

62309

83079

103849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15888

31776

47664

63552

79440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.450

AC:

68291

AN:

151848

Hom.:

15694

Cov.:

AF XY:

0.452

AC XY:

33519

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.393

AC:

16262

AN:

41392

American (AMR)

AF:

0.360

AC:

5484

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

1650

AN:

3468

East Asian (EAS)

AF:

0.371

AC:

1911

AN:

5152

South Asian (SAS)

AF:

0.550

AC:

2645

AN:

4810

European-Finnish (FIN)

AF:

0.533

AC:

5610

AN:

10528

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.487

AC:

33068

AN:

67942

Other (OTH)

AF:

0.449

AC:

945

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1972

3944

5917

7889

9861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hearing loss, autosomal recessive 112 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.057

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.091

MetaRNN

Benign

0.000025

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.9

PhyloP100

-0.071

PrimateAI

Benign

0.32

PROVEAN

Benign

0.93

REVEL

Benign

0.0040

Sift

Benign

1.0

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.037

MPC

0.046

ClinPred

0.00016

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.020

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over