rs4580655

Variant names:

• chr4-103608117-G-A
• rs4580655
• NM_001059.3:c.889-16434C>T

Variant summary

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

The NM_001059.3(TACR3):​c.889-16434C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,890 control chromosomes in the GnomAD database, including 29,932 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 0.62 (29932 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 6 publications found

Genes affected

TACR3 (HGNC:11528): (tachykinin receptor 3) 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 neurokinin 3, also referred to as neurokinin B. [provided by RefSeq, Jul 2008]

TACR3-AS1 (HGNC:55593): (TACR3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.889-16434C>T		intron_variant	Intron 3 of 4	ENST00000304883.3	NP_001050.1
TACR3-AS1	NR_186501.1	n.571+14685G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.889-16434C>T		intron_variant	Intron 3 of 4	1	NM_001059.3	ENSP00000303325.2
TACR3-AS1	ENST00000502936.1	n.571+14685G>A		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94830 AN: 151772 Hom.: 29904 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.625 AC: 94900 AN: 151890 Hom.: 29932 Cov.: 32 AF XY: 0.625 AC XY: 46409 AN XY: 74238

African (AFR) AF: 0.587 AC: 24296 AN: 41410

American (AMR) AF: 0.627 AC: 9553 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2320 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2467 AN: 5164

South Asian (SAS) AF: 0.458 AC: 2202 AN: 4804

European-Finnish (FIN) AF: 0.758 AC: 8022 AN: 10584

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43879 AN: 67918

Other (OTH) AF: 0.621 AC: 1306 AN: 2104

Alfa AF: 0.636 Hom.: 5409

Bravo AF: 0.618

Asia WGS AF: 0.480 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.38
PhyloP100		-0.54
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: rs4580655; hg19: chr4-104529274;