Variant 10-91951543-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_003972.3(BTAF1):c.541G>T(p.Ala181Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00236 in 1,602,414 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 16 hom. )

Consequence

BTAF1
NM_003972.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

BTAF1 (HGNC:17307): (B-TFIID TATA-box binding protein associated factor 1) This gene encodes a TAF (TATA box-binding protein-associated factor), which associates with TBP (TATA box-binding protein) to form the B-TFIID complex that is required for transcription initiation of genes by RNA polymerase II. This TAF has DNA-dependent ATPase activity, which drives the dissociation of TBP from DNA, freeing the TBP to associate with other TATA boxes or TATA-less promoters. [provided by RefSeq, Sep 2011]

BTAF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, BTAF1

BP4

Computational evidence support a benign effect (MetaRNN=0.003952384).

BS2

High AC in GnomAd4 at 259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTAF1	NM_003972.3 linkuse as main transcript	c.541G>T	p.Ala181Ser	missense_variant	5/38	ENST00000265990.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTAF1	ENST00000265990.12 linkuse as main transcript	c.541G>T	p.Ala181Ser	missense_variant	5/38	1	NM_003972.3	P1	O14981-1

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

259

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00231

AC:

555

AN:

239868

Hom.:

AF XY:

0.00283

AC XY:

366

AN XY:

129366

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000705

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00864

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.00243

AC:

3525

AN:

1450096

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

1902

AN XY:

720530

show subpopulations

Gnomad4 AFR exome

AF:

0.000274

Gnomad4 AMR exome

AF:

0.000907

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00925

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00227

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00170

AC:

259

AN:

152318

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00931

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00257

AC:

312

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.541G>T (p.A181S) alteration is located in exon 5 (coding exon 5) of the BTAF1 gene. This alteration results from a G to T substitution at nucleotide position 541, causing the alanine (A) at amino acid position 181 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.066

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

-0.46

N;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.42

PROVEAN

Benign

0.20

N;.

REVEL

Benign

0.25

Sift

Benign

0.77

T;.

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;.

Vest4

0.15

MVP

0.43

MPC

0.44

ClinPred

0.0036

GERP RS

4.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Varity_R

0.050

gMVP

0.14

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