chr2-75186888-G-A

Variant names:

• chr2-75186888-G-A
• rs3771856
• NM_001058.4:c.389+11658C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 5 publications found

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]

ENSG00000270571 (HGNC:58209):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	NM_001058.4	MANE Select	c.389+11658C>T		intron	N/A	NP_001049.1
	TACR1-AS1	NR_168011.1		n.425G>A		non_coding_transcript_exon	Exon 3 of 3
	TACR1	NM_015727.3		c.389+11658C>T		intron	N/A	NP_056542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	ENST00000305249.10	TSL:1 MANE Select	c.389+11658C>T		intron	N/A	ENSP00000303522.4
	TACR1	ENST00000409848.3	TSL:1	c.389+11658C>T		intron	N/A	ENSP00000386448.3
	ENSG00000270571	ENST00000604271.2	TSL:4	n.377G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85179 AN: 151998 Hom.: 26319 Cov.: 33

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: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ 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.

GnomAD4 genome AF: 0.561 AC: 85276 AN: 152116 Hom.: 26355 Cov.: 33 AF XY: 0.554 AC XY: 41171 AN XY: 74340

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.41
PhyloP100		-0.013
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3771856; hg19: chr2-75414014;