Genetic Variant BTAF1:p.Ile49Met (chr10-91939960-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003972.3(BTAF1):c.147A>G(p.Ile49Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,606,816 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

BTAF1
NM_003972.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.900

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16555697).

BS2

High AC in GnomAdExome4 at 41 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003972.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTAF1	NM_003972.3	MANE Select	c.147A>G	p.Ile49Met	missense	Exon 3 of 38	NP_003963.1	Q2M1V9
BTAF1	NR_165090.1		n.454A>G		non_coding_transcript_exon	Exon 3 of 37
BTAF1	NR_165091.1		n.454A>G		non_coding_transcript_exon	Exon 3 of 39

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTAF1	ENST00000265990.12	TSL:1 MANE Select	c.147A>G	p.Ile49Met	missense	Exon 3 of 38	ENSP00000265990.6	O14981-1
BTAF1	ENST00000928671.1		c.147A>G	p.Ile49Met	missense	Exon 3 of 37	ENSP00000598730.1
BTAF1	ENST00000928669.1		c.147A>G	p.Ile49Met	missense	Exon 3 of 37	ENSP00000598728.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250804

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1454664

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

723936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33334

American (AMR)

AF:

0.0000224

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.00

AC:

AN:

85506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53160

Middle Eastern (MID)

AF:

0.00575

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000542

AC:

AN:

1106700

Other (OTH)

AF:

0.0000166

AC:

AN:

60062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000131

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.14

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.78

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.90

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.20

REVEL

Benign

0.053

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.21

Vest4

0.18

MVP

0.26

MPC

0.62

ClinPred

0.092

GERP RS

2.0

Varity_R

0.042

gMVP

0.19

Mutation Taster

=94/6

polymorphism

(source)

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

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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