5-71455991-T-G

Position:

chr5-71455991-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018429.3(BDP1):c.114T>G(p.Asp38Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,613,142 control chromosomes in the GnomAD database, including 549,699 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 (★★).

Frequency

Genomes: 𝑓 0.77 ( 46347 hom., cov: 32)

Exomes 𝑓: 0.83 ( 503352 hom. )

Consequence

BDP1
NM_018429.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.747

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=6.569157E-7).

BP6

Variant 5-71455991-T-G is Benign according to our data. Variant chr5-71455991-T-G is described in ClinVar as [Benign]. Clinvar id is 508084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDP1	NM_018429.3 link	c.114T>G	p.Asp38Glu	missense_variant	1/39	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.114T>G	p.Asp38Glu	missense_variant	1/39	1	NM_018429.3	ENSP00000351575.4		A6H8Y1-1
BDP1	ENST00000508917.6 link	n.306T>G		non_coding_transcript_exon_variant	1/32	1

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117628

AN:

152038

Hom.:

46332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.609

Gnomad AMI

AF:

0.822

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.888

Gnomad EAS

AF:

0.880

Gnomad SAS

AF:

0.839

Gnomad FIN

AF:

0.808

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.830

Gnomad OTH

AF:

0.805

GnomAD3 exomes

AF:

0.831

AC:

204797

AN:

246372

Hom.:

85729

AF XY:

0.831

AC XY:

111742

AN XY:

134406

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.899

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.885

Gnomad SAS exome

AF:

0.829

Gnomad FIN exome

AF:

0.819

Gnomad NFE exome

AF:

0.830

Gnomad OTH exome

AF:

0.844

GnomAD4 exome

AF:

0.829

AC:

1210828

AN:

1460986

Hom.:

503352

Cov.:

AF XY:

0.829

AC XY:

602661

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.593

Gnomad4 AMR exome

AF:

0.893

Gnomad4 ASJ exome

AF:

0.896

Gnomad4 EAS exome

AF:

0.878

Gnomad4 SAS exome

AF:

0.827

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.831

Gnomad4 OTH exome

AF:

0.826

GnomAD4 genome

AF:

0.774

AC:

117697

AN:

152156

Hom.:

46347

Cov.:

AF XY:

0.776

AC XY:

57722

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.609

Gnomad4 AMR

AF:

0.852

Gnomad4 ASJ

AF:

0.888

Gnomad4 EAS

AF:

0.880

Gnomad4 SAS

AF:

0.841

Gnomad4 FIN

AF:

0.808

Gnomad4 NFE

AF:

0.830

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.819

Hom.:

52994

Bravo

AF:

0.770

TwinsUK

AF:

0.833

AC:

3088

ALSPAC

AF:

0.844

AC:

3253

ESP6500AA

AF:

0.627

AC:

2390

ESP6500EA

AF:

0.832

AC:

6851

ExAC

AF:

0.822

AC:

99107

Asia WGS

AF:

0.824

AC:

2867

AN:

3478

EpiCase

AF:

0.831

EpiControl

AF:

0.827

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

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. -

Hearing loss, autosomal recessive 112

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.4

DANN

Benign

0.70

DEOGEN2

Benign

0.0033

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.10

T;T

MetaRNN

Benign

6.6e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.5

N;.

PrimateAI

Benign

0.46

PROVEAN

Benign

0.95

N;.

REVEL

Benign

0.067

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.047

MutPred

0.098

Gain of glycosylation at P36 (P = 0.0911);Gain of glycosylation at P36 (P = 0.0911);

MPC

0.036

ClinPred

0.0046

GERP RS

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.032

gMVP

0.023

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