chr5-71539065-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_018429.3(BDP1):c.5916C>A(p.Ile1972Ile) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.250

Publications

9 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 -19 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 VariationId is 508602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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.5916C>A	p.Ile1972Ile	synonymous	Exon 27 of 39	NP_060899.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BDP1	ENST00000358731.9	TSL:1 MANE Select	c.5916C>A	p.Ile1972Ile	synonymous	Exon 27 of 39	ENSP00000351575.4
BDP1	ENST00000508917.6	TSL:1	n.6108C>A		non_coding_transcript_exon	Exon 27 of 32
BDP1	ENST00000525844.1	TSL:1	n.78C>A		non_coding_transcript_exon	Exon 2 of 14	ENSP00000432404.1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3804

AN:

152030

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0321

AC:

7825

AN:

244140

AF XY:

0.0336

show subpopulations

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 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.:

AF XY:

0.0286

AC XY:

20637

AN XY:

720324

show subpopulations

African (AFR)

AF:

0.00870

AC:

288

AN:

33118

American (AMR)

AF:

0.0366

AC:

1568

AN:

42886

Ashkenazi Jewish (ASJ)

AF:

0.0250

AC:

647

AN:

25928

East Asian (EAS)

AF:

0.00814

AC:

321

AN:

39444

South Asian (SAS)

AF:

0.0650

AC:

5494

AN:

84514

European-Finnish (FIN)

AF:

0.0360

AC:

1922

AN:

53348

Middle Eastern (MID)

AF:

0.0288

AC:

165

AN:

5728

European-Non Finnish (NFE)

AF:

0.0251

AC:

27684

AN:

1102204

Other (OTH)

AF:

0.0256

AC:

1531

AN:

59888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

1654

3308

4961

6615

8269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1042

2084

3126

4168

5210

<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:

0.0250

AC:

3805

AN:

152148

Hom.:

Cov.:

AF XY:

0.0257

AC XY:

1909

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0115

AC:

479

AN:

41502

American (AMR)

AF:

0.0305

AC:

466

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.0139

AC:

AN:

5180

South Asian (SAS)

AF:

0.0735

AC:

354

AN:

4814

European-Finnish (FIN)

AF:

0.0381

AC:

403

AN:

10576

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0278

AC:

1891

AN:

68004

Other (OTH)

AF:

0.0232

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

193

386

580

773

966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0254

Hom.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 28, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

7.0

(source)

DANN

Benign

0.74

PhyloP100

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over