rs2421013

Positions:

• chr10-122329521-G-A
• chr10-122329521-G-C
• chr10-122329521-G-T

Variant summary

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

The NM_144587.5(BTBD16):​c.953G>A​(p.Arg318Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,140 control chromosomes in the GnomAD database, including 231,016 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.

• Frequency:
  • Genomes: 𝑓 0.56 (23813 hom., cov: 33)
  • Exomes 𝑓: 0.53 (207203 hom.)
• Consequence: BTBD16 NM_144587.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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=1.1026592E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD16	NM_144587.5	c.953G>A	p.Arg318Gln	missense_variant	11/16	ENST00000260723.6	NP_653188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD16	ENST00000260723.6	c.953G>A	p.Arg318Gln	missense_variant	11/16	2	NM_144587.5	ENSP00000260723.4

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84389 AN: 151922 Hom.: 23784 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.540

GnomAD3 exomes AF: 0.563 AC: 141297 AN: 251054 Hom.: 41241 AF XY: 0.552 AC XY: 74934 AN XY: 135702

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.514

Gnomad EAS exome AF: 0.860

Gnomad SAS exome AF: 0.495

Gnomad FIN exome AF: 0.593

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.542

GnomAD4 exome AF: 0.528 AC: 770788 AN: 1461100 Hom.: 207203 Cov.: 50 AF XY: 0.526 AC XY: 382126 AN XY: 726872

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.886

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.556 AC: 84459 AN: 152040 Hom.: 23813 Cov.: 33 AF XY: 0.561 AC XY: 41696 AN XY: 74310

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.545

Alfa AF: 0.523 Hom.: 52634

Bravo AF: 0.563

TwinsUK AF: 0.502 AC: 1863

ALSPAC AF: 0.498 AC: 1919

ESP6500AA AF: 0.605 AC: 2667

ESP6500EA AF: 0.511 AC: 4394

ExAC AF: 0.561 AC: 68083

Asia WGS AF: 0.686 AC: 2384 AN: 3478

EpiCase AF: 0.502

EpiControl AF: 0.512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.18
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.055
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.015
MPC		0.16
ClinPred		0.0038	T
GERP RS		4.6
Varity_R		0.028
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2421013; hg19: chr10-124089036; COSMIC: COSV53261869; COSMIC: COSV53261869;