dbSNP rs1048347: BTBD16:p.His439Pro (chr10-122336546-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144587.5(BTBD16):c.1316A>C(p.His439Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,608,328 control chromosomes in the GnomAD database, including 102,119 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H439N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.37 ( 10683 hom., cov: 33)

Exomes 𝑓: 0.34 ( 91436 hom. )

Consequence

BTBD16
NM_144587.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0910

Publications

26 publications found

Variant links:

Genes affected

BTBD16 (HGNC:26340): (BTB domain containing 16) This gene encodes a protein that contains a BTB/POZ domain. This domain mediates protein-protein interactions. A mutation in this gene may be associated with bipolar disorder. [provided by RefSeq, Sep 2016]

BTBD16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.5271257E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD16	NM_144587.5 link	c.1316A>C	p.His439Pro	missense_variant	Exon 15 of 16	ENST00000260723.6	NP_653188.2	Q32M84-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD16	ENST00000260723.6 link	c.1316A>C	p.His439Pro	missense_variant	Exon 15 of 16	2	NM_144587.5	ENSP00000260723.4		Q32M84-1
BTBD16	ENST00000495370.2 link	n.522A>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55669

AN:

151870

Hom.:

10656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.353

GnomAD2 exomes

AF:

0.397

AC:

98377

AN:

247864

AF XY:

0.390

show subpopulations

Gnomad AFR exome

AF:

0.362

Gnomad AMR exome

AF:

0.530

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.687

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.343

AC:

498943

AN:

1456340

Hom.:

91436

Cov.:

AF XY:

0.344

AC XY:

249150

AN XY:

724656

show subpopulations

African (AFR)

AF:

0.365

AC:

12106

AN:

33198

American (AMR)

AF:

0.516

AC:

22495

AN:

43632

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

7639

AN:

26034

East Asian (EAS)

AF:

0.739

AC:

29202

AN:

39536

South Asian (SAS)

AF:

0.409

AC:

34989

AN:

85612

European-Finnish (FIN)

AF:

0.422

AC:

22500

AN:

53344

Middle Eastern (MID)

AF:

0.364

AC:

2095

AN:

5762

European-Non Finnish (NFE)

AF:

0.312

AC:

346304

AN:

1108998

Other (OTH)

AF:

0.359

AC:

21613

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

16898

33796

50693

67591

84489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11500

23000

34500

46000

57500

<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:

0.367

AC:

55735

AN:

151988

Hom.:

10683

Cov.:

AF XY:

0.376

AC XY:

27953

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.364

AC:

15089

AN:

41434

American (AMR)

AF:

0.446

AC:

6804

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1010

AN:

3468

East Asian (EAS)

AF:

0.694

AC:

3577

AN:

5156

South Asian (SAS)

AF:

0.417

AC:

2009

AN:

4812

European-Finnish (FIN)

AF:

0.418

AC:

4421

AN:

10572

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.321

AC:

21799

AN:

67972

Other (OTH)

AF:

0.361

AC:

761

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1806

3611

5417

7222

9028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.334

Hom.:

37223

Bravo

AF:

0.370

TwinsUK

AF:

0.308

AC:

1142

ALSPAC

AF:

0.297

AC:

1145

ESP6500AA

AF:

0.359

AC:

1583

ESP6500EA

AF:

0.322

AC:

2766

ExAC

AF:

0.394

AC:

47885

Asia WGS

AF:

0.566

AC:

1968

AN:

3478

EpiCase

AF:

0.315

EpiControl

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.20

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.00098

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00088

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0000055

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.4

PhyloP100

0.091

PrimateAI

Benign

0.27

PROVEAN

Benign

1.6

REVEL

Benign

0.024

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.044

MPC

0.22

ClinPred

0.0067

GERP RS

1.4

Varity_R

0.054

gMVP

0.17

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over