dbSNP rs3771856: TACR1:c.389+11658C>T (chr2-75186888-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001058.4(TACR1):c.389+11658C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,118 control chromosomes in the GnomAD database, including 26,355 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 26355 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

TACR1
NM_001058.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0130

Publications

5 publications found

Variant links:

Genes affected

TACR1 (HGNC:11526): (tachykinin receptor 1) This gene belongs to a gene family of tachykinin receptors. These tachykinin receptors are characterized by interactions with G proteins and contain seven hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin substance P, also referred to as neurokinin 1. The encoded protein is also involved in the mediation of phosphatidylinositol metabolism of substance P. [provided by RefSeq, Sep 2008]

TACR1 links:

ENSG00000270571 (HGNC:58209):

ENSG00000270571 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 (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4 link	c.389+11658C>T		intron_variant	Intron 1 of 4	ENST00000305249.10	NP_001049.1	P25103-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TACR1	ENST00000305249.10 link	c.389+11658C>T	intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4	P25103-1
TACR1	ENST00000409848.3 link	c.389+11658C>T	intron_variant	Intron 1 of 3	1		ENSP00000386448.3	P25103-3
ENSG00000270571	ENST00000604271.2 link	n.377G>A	non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85179

AN:

151998

Hom.:

26319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.462

Gnomad OTH

AF:

0.529

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.561

AC:

85276

AN:

152116

Hom.:

26355

Cov.:

AF XY:

0.554

AC XY:

41171

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.847

AC:

35157

AN:

41512

American (AMR)

AF:

0.476

AC:

7277

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1300

AN:

3468

East Asian (EAS)

AF:

0.432

AC:

2230

AN:

5166

South Asian (SAS)

AF:

0.391

AC:

1882

AN:

4818

European-Finnish (FIN)

AF:

0.429

AC:

4533

AN:

10564

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.462

AC:

31390

AN:

67994

Other (OTH)

AF:

0.527

AC:

1109

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1748

3497

5245

6994

8742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.521

Hom.:

2745

Bravo

AF:

0.580

Asia WGS

AF:

0.449

AC:

1560

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.4

(source)

DANN

Benign

0.41

PhyloP100

-0.013

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over