rs1048347

Positions:

• chr10-122336546-A-C
• chr10-122336546-A-G
• chr10-122336546-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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]

ACMG classification

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/exons	MANE	UniProt
BTBD16	NM_144587.5	c.1316A>C	p.His439Pro	missense_variant	15/16	ENST00000260723.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD16	ENST00000260723.6	c.1316A>C	p.His439Pro	missense_variant	15/16	2	NM_144587.5	P1
BTBD16	ENST00000495370.2	n.522A>C		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55669 AN: 151870 Hom.: 10656 Cov.: 33

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

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.: 35 AF XY: 0.344 AC XY: 249150 AN XY: 724656

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.: 33 AF XY: 0.376 AC XY: 27953 AN XY: 74302

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	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.39
DEOGEN2	Benign	0.00098	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00088	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000055	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.4	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.044
MPC		0.22
ClinPred		0.0067	T
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

Other links and lift over

dbSNP: rs1048347; hg19: chr10-124096061; COSMIC: COSV53262086;