Genetic Variant BDP1:c.599+45_599+53delTTTTTTTTT (chr5-71461958-CTTTTTTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018429.3(BDP1):c.599+45_599+53delTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 444,100 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

BDP1
NM_018429.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.77

Publications

0 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
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

BDP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	NM_018429.3	MANE Select	c.599+45_599+53delTTTTTTTTT		intron	N/A	NP_060899.2	A6H8Y1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	ENST00000358731.9	TSL:1 MANE Select	c.599+33_599+41delTTTTTTTTT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+33_791+41delTTTTTTTTT		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000917

AC:

AN:

109076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000174

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000448

AC:

AN:

335024

Hom.:

AF XY:

0.0000435

AC XY:

AN XY:

183726

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000117

AC:

AN:

8514

American (AMR)

AF:

0.00

AC:

AN:

15736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8756

East Asian (EAS)

AF:

0.00

AC:

AN:

16474

South Asian (SAS)

AF:

0.0000960

AC:

AN:

41680

European-Finnish (FIN)

AF:

0.0000477

AC:

AN:

20974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1122

European-Non Finnish (NFE)

AF:

0.0000438

AC:

AN:

205490

Other (OTH)

AF:

0.00

AC:

AN:

16278

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000334889), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.362

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000917

AC:

AN:

109076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

49498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28858

American (AMR)

AF:

0.00

AC:

AN:

8082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3050

East Asian (EAS)

AF:

0.00

AC:

AN:

3758

South Asian (SAS)

AF:

0.00

AC:

AN:

3290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

164

European-Non Finnish (NFE)

AF:

0.0000174

AC:

AN:

57334

Other (OTH)

AF:

0.00

AC:

AN:

1426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

909

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-71461958-CTTTTTTTTTTTTT-CTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over