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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.397

AC:

98377

AN:

247864

Hom.:

21432

AF XY:

0.390

AC XY:

52306

AN XY:

134182

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 SAS exome

AF:

0.413

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

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.739

Gnomad4 SAS exome

AF:

0.409

Gnomad4 FIN exome

AF:

0.422

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.367

AC:

55735

AN:

151988

Hom.:

10683

Cov.:

AF XY:

0.376

AC XY:

27953

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.694

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.324

Hom.:

15423

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over