dbSNP rs7448990: BDP1:c.213-472G>A (chr5-71458107-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018429.3(BDP1):c.213-472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,988 control chromosomes in the GnomAD database, including 16,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16660 hom., cov: 32)

Consequence

BDP1
NM_018429.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDP1	NM_018429.3 link	c.213-472G>A		intron_variant	Intron 1 of 38	ENST00000358731.9	NP_060899.2	A6H8Y1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9 link	c.213-472G>A		intron_variant	Intron 1 of 38	1	NM_018429.3	ENSP00000351575.4		A6H8Y1-1
BDP1	ENST00000508917.6 link	n.405-472G>A		intron_variant	Intron 1 of 31	1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70550

AN:

151870

Hom.:

16651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.459

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.464

AC:

70595

AN:

151988

Hom.:

16660

Cov.:

AF XY:

0.466

AC XY:

34597

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.446

AC:

18508

AN:

41458

American (AMR)

AF:

0.364

AC:

5552

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1640

AN:

3466

East Asian (EAS)

AF:

0.370

AC:

1918

AN:

5180

South Asian (SAS)

AF:

0.548

AC:

2642

AN:

4820

European-Finnish (FIN)

AF:

0.532

AC:

5594

AN:

10516

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.486

AC:

33055

AN:

67970

Other (OTH)

AF:

0.458

AC:

968

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1946

3892

5839

7785

9731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.460

Hom.:

3515

Bravo

AF:

0.445

Asia WGS

AF:

0.449

AC:

1561

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

4.2

(source)

DANN

Benign

0.58

PhyloP100

1.4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over