5-71458740-C-T

Position:

chr5-71458740-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018429.3(BDP1):c.374C>T(p.Ala125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,614,064 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.013 ( 47 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 35 hom. )

Consequence

BDP1
NM_018429.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.239

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020684302).

BP6

Variant 5-71458740-C-T is Benign according to our data. Variant chr5-71458740-C-T is described in ClinVar as [Benign]. Clinvar id is 684104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1917/152226) while in subpopulation AFR AF= 0.0434 (1802/41542). AF 95% confidence interval is 0.0417. There are 47 homozygotes in gnomad4. There are 901 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDP1	NM_018429.3 link	c.374C>T	p.Ala125Val	missense_variant	2/39	ENST00000358731.9	NP_060899.2	A6H8Y1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9 link	c.374C>T	p.Ala125Val	missense_variant	2/39	1	NM_018429.3	ENSP00000351575.4		A6H8Y1-1
BDP1	ENST00000508917.6 link	n.566C>T		non_coding_transcript_exon_variant	2/32	1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1916

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00295

AC:

736

AN:

249496

Hom.:

AF XY:

0.00238

AC XY:

322

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00123

AC:

1791

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

757

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.0126

AC:

1917

AN:

152226

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

901

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0434

Gnomad4 AMR

AF:

0.00563

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.0144

ESP6500AA

AF:

0.0425

AC:

162

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.00367

AC:

444

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.98

DANN

Benign

0.97

DEOGEN2

Benign

0.0059

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.78

N;.

REVEL

Benign

0.023

Sift

Benign

0.29

T;.

Sift4G

Benign

0.29

T;T

Polyphen

0.060

B;.

Vest4

0.068

MVP

0.040

MPC

0.041

ClinPred

0.0016

GERP RS

0.066

Varity_R

0.016

gMVP

0.056

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