dbSNP rs5030920: TACR2:p.Ile23Thr (chr10-69416256-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001057.3(TACR2):c.68T>C(p.Ile23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,236 control chromosomes in the GnomAD database, including 45,413 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.

Frequency

Genomes: 𝑓 0.26 ( 5661 hom., cov: 33)

Exomes 𝑓: 0.23 ( 39752 hom. )

Consequence

TACR2
NM_001057.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0150

Publications

22 publications found

Variant links:

Genes affected

TACR2 (HGNC:11527): (tachykinin receptor 2) This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neuropeptide substance K, also referred to as neurokinin A. [provided by RefSeq, Jul 2008]

TACR2 links:

ENSG00000299486 (HGNC:):

ENSG00000299486 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=0.007045418).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR2	NM_001057.3	MANE Select	c.68T>C	p.Ile23Thr	missense	Exon 1 of 5	NP_001048.2	P21452

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR2	ENST00000373306.5	TSL:1 MANE Select	c.68T>C	p.Ile23Thr	missense	Exon 1 of 5	ENSP00000362403.4	P21452
	ENSG00000299486	ENST00000763854.1		n.85-8924A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38986

AN:

152052

Hom.:

5665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.0412

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.245

GnomAD2 exomes

AF:

0.213

AC:

53553

AN:

251094

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.0386

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.227

AC:

332226

AN:

1461066

Hom.:

39752

Cov.:

AF XY:

0.229

AC XY:

166113

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.388

AC:

12980

AN:

33470

American (AMR)

AF:

0.150

AC:

6716

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

5703

AN:

26122

East Asian (EAS)

AF:

0.0224

AC:

889

AN:

39686

South Asian (SAS)

AF:

0.287

AC:

24780

AN:

86224

European-Finnish (FIN)

AF:

0.194

AC:

10302

AN:

53230

Middle Eastern (MID)

AF:

0.262

AC:

1511

AN:

5764

European-Non Finnish (NFE)

AF:

0.230

AC:

255154

AN:

1111496

Other (OTH)

AF:

0.235

AC:

14191

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16274

32548

48821

65095

81369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8814

17628

26442

35256

44070

<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:

0.256

AC:

39007

AN:

152170

Hom.:

5661

Cov.:

AF XY:

0.250

AC XY:

18632

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.379

AC:

15732

AN:

41498

American (AMR)

AF:

0.183

AC:

2798

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

806

AN:

3470

East Asian (EAS)

AF:

0.0413

AC:

214

AN:

5184

South Asian (SAS)

AF:

0.284

AC:

1368

AN:

4820

European-Finnish (FIN)

AF:

0.183

AC:

1938

AN:

10600

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15426

AN:

67990

Other (OTH)

AF:

0.243

AC:

514

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1429

2858

4288

5717

7146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.235

Hom.:

11847

Bravo

AF:

0.257

TwinsUK

AF:

0.227

AC:

842

ALSPAC

AF:

0.238

AC:

916

ESP6500AA

AF:

0.374

AC:

1649

ESP6500EA

AF:

0.224

AC:

1930

ExAC

AF:

0.221

AC:

26841

Asia WGS

AF:

0.163

AC:

569

AN:

3478

EpiCase

AF:

0.228

EpiControl

AF:

0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.3

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

PhyloP100

-0.015

PrimateAI

Benign

0.33

PROVEAN

Benign

0.95

REVEL

Benign

0.019

Sift

Benign

0.64

Sift4G

Uncertain

0.0080

Polyphen

0.0

Vest4

0.016

MPC

0.34

ClinPred

0.00088

GERP RS

2.8

Varity_R

0.019

gMVP

0.21

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over