Variant rs199721728 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018429.3(BDP1):c.7873T>G(p.Ter2625GluextTer11) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,583,314 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 3 hom. )

Consequence

BDP1
NM_018429.3 stop_lost

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 2.62

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.613886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDP1	NM_018429.3 linkuse as main transcript	c.7873T>G	p.Ter2625GluextTer11	stop_lost	39/39	ENST00000358731.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDP1	ENST00000358731.9 linkuse as main transcript	c.7873T>G	p.Ter2625GluextTer11	stop_lost	39/39	1	NM_018429.3	P1	A6H8Y1-1
BDP1	ENST00000525844.1 linkuse as main transcript	c.*239T>G		3_prime_UTR_variant, NMD_transcript_variant	14/14	1
BDP1	ENST00000514903.7 linkuse as main transcript	c.*823T>G		3_prime_UTR_variant, NMD_transcript_variant	16/16	5

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000872

AC:

196

AN:

224672

Hom.:

AF XY:

0.000962

AC XY:

118

AN XY:

122698

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000153

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000632

AC:

905

AN:

1430996

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

477

AN XY:

711394

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000139

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00106

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000413

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000558

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000635

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00111

AC:

ExAC

AF:

0.000770

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hearing loss, autosomal recessive 112

Pathogenic:1Benign:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Jul 30, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Mar 26, 2024	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 05, 2021

This variant is associated with the following publications: (PMID: 27884173, 24312468, 25060281) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.77

Eigen

Pathogenic

0.79

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.82

MutationTaster

Benign

0.85

D;N

Vest4

0.070

GERP RS

4.5

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over