rs4439987

Positions:

• chr2-75059979-G-A
• chr2-75059979-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001058.4(TACR1):​c.585-6224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,198 control chromosomes in the GnomAD database, including 35,148 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 0.66 (35148 hom., cov: 34)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.585-6224C>T		intron_variant		ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.585-6224C>T		intron_variant			NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.585-6224C>T		intron_variant		1	NM_001058.4	ENSP00000303522	P1
TACR1	ENST00000409848.3	c.585-6224C>T		intron_variant		1		ENSP00000386448

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100336 AN: 152080 Hom.: 35087 Cov.: 34

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.660 AC: 100460 AN: 152198 Hom.: 35148 Cov.: 34 AF XY: 0.659 AC XY: 49056 AN XY: 74406

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.637

Alfa AF: 0.565 Hom.: 35222

Bravo AF: 0.678

Asia WGS AF: 0.747 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs4439987; hg19: chr2-75287106;