rs2421013

Variant names:

• chr10-122329521-G-A
• rs2421013
• NM_144587.5:c.953G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 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. R318W) has been classified as Uncertain significance.

• 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
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BTBD16	NM_144587.5	c.953G>A	p.Arg318Gln	missense_variant	Exon 11 of 16	ENST00000260723.6	NP_653188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD16	ENST00000260723.6	c.953G>A	p.Arg318Gln	missense_variant	Exon 11 of 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

GnomAD2 exomes AF: 0.563 AC: 141297 AN: 251054 AF XY: 0.552

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 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

African (AFR) AF: 0.601 AC: 20101 AN: 33466

American (AMR) AF: 0.617 AC: 27579 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 13526 AN: 26120

East Asian (EAS) AF: 0.886 AC: 35168 AN: 39688

South Asian (SAS) AF: 0.497 AC: 42889 AN: 86212

European-Finnish (FIN) AF: 0.588 AC: 31276 AN: 53172

Middle Eastern (MID) AF: 0.581 AC: 3348 AN: 5762

European-Non Finnish (NFE) AF: 0.507 AC: 563934 AN: 1111612

Other (OTH) AF: 0.546 AC: 32967 AN: 60372

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

African (AFR) AF: 0.603 AC: 25018 AN: 41456

American (AMR) AF: 0.572 AC: 8743 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1765 AN: 3472

East Asian (EAS) AF: 0.864 AC: 4463 AN: 5164

South Asian (SAS) AF: 0.507 AC: 2444 AN: 4824

European-Finnish (FIN) AF: 0.588 AC: 6223 AN: 10582

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.502 AC: 34110 AN: 67944

Other (OTH) AF: 0.545 AC: 1151 AN: 2112

Alfa AF: 0.528 Hom.: 74621

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
PhyloP100		1.5
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2421013; hg19: chr10-124089036; COSMIC: COSV53261869; COSMIC: COSV53261869;