rs34768748

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018429.3(BDP1):c.5784T>G(p.Thr1928Thr) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.26

Publications

1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDP1	NM_018429.3 link	c.5784T>G	p.Thr1928Thr	synonymous_variant	Exon 26 of 39	ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
BDP1	ENST00000358731.9 link	c.5784T>G	p.Thr1928Thr	synonymous_variant	Exon 26 of 39	1	NM_018429.3	ENSP00000351575.4
BDP1	ENST00000508917.6 link	n.5976T>G		non_coding_transcript_exon_variant	Exon 26 of 32	1
BDP1	ENST00000514903.7 link	n.552T>G		non_coding_transcript_exon_variant	Exon 3 of 16	5		ENSP00000421910.3
BDP1	ENST00000525844.1 link	n.-55T>G		upstream_gene_variant		1		ENSP00000432404.1

Frequencies

GnomAD3 genomes

AF:

0.00990

AC:

1507

AN:

152218

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00253

AC:

629

AN:

248992

AF XY:

0.00182

show subpopulations

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 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.:

Cov.:

AF XY:

0.000710

AC XY:

516

AN XY:

726792

show subpopulations

African (AFR)

AF:

0.0296

AC:

989

AN:

33450

American (AMR)

AF:

0.00248

AC:

111

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1111606

Other (OTH)

AF:

0.00204

AC:

123

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00990

AC:

1508

AN:

152336

Hom.:

Cov.:

AF XY:

0.00954

AC XY:

711

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0341

AC:

1419

AN:

41572

American (AMR)

AF:

0.00458

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68028

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00541

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 29, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.093

(source)

DANN

Benign

0.50

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over