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GeneBe

2-75049522-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001058.4(TACR1):c.1134G>A(p.Ser378=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00901 in 1,614,160 control chromosomes in the GnomAD database, including 532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 201 hom., cov: 33)
Exomes 𝑓: 0.0068 ( 331 hom. )

Consequence

TACR1
NM_001058.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.65
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-75049522-C-T is Benign according to our data. Variant chr2-75049522-C-T is described in ClinVar as [Benign]. Clinvar id is 3059844.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.65 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TACR1NM_001058.4 linkuse as main transcriptc.1134G>A p.Ser378= synonymous_variant 5/5 ENST00000305249.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TACR1ENST00000305249.10 linkuse as main transcriptc.1134G>A p.Ser378= synonymous_variant 5/51 NM_001058.4 P1P25103-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0302
AC:
4594
AN:
152220
Hom.:
200
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0908
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0129
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0584
Gnomad SAS
AF:
0.0512
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000529
Gnomad OTH
AF:
0.0201
GnomAD3 exomes
AF:
0.0167
AC:
4202
AN:
251054
Hom.:
150
AF XY:
0.0161
AC XY:
2178
AN XY:
135694
show subpopulations
Gnomad AFR exome
AF:
0.0954
Gnomad AMR exome
AF:
0.00338
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0619
Gnomad SAS exome
AF:
0.0414
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000608
Gnomad OTH exome
AF:
0.0104
GnomAD4 exome
AF:
0.00680
AC:
9946
AN:
1461822
Hom.:
331
Cov.:
31
AF XY:
0.00749
AC XY:
5448
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.0933
Gnomad4 AMR exome
AF:
0.00476
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0501
Gnomad4 SAS exome
AF:
0.0398
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000376
Gnomad4 OTH exome
AF:
0.0121
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0302
AC:
4603
AN:
152338
Hom.:
201
Cov.:
33
AF XY:
0.0295
AC XY:
2201
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0908
Gnomad4 AMR
AF:
0.0129
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0586
Gnomad4 SAS
AF:
0.0512
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000529
Gnomad4 OTH
AF:
0.0198
Alfa
AF:
0.0162
Hom.:
57
Bravo
AF:
0.0331
Asia WGS
AF:
0.0560
AC:
194
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TACR1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 18, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
0.042
Dann
Benign
0.49

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34117315; hg19: chr2-75276649; COSMIC: COSV59480205; COSMIC: COSV59480205; API