rs7663664

Variant names:

• chr4-103663678-G-A
• rs7663664
• NM_001059.3:c.549-5275C>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.549-5275C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,000 control chromosomes in the GnomAD database, including 17,206 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 0.43 (17206 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• Publications: 4 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 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 11 with or without anosmia

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.549-5275C>T		intron_variant	Intron 1 of 4	ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.549-5275C>T		intron_variant	Intron 1 of 4	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65727 AN: 151882 Hom.: 17163 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.433 AC: 65822 AN: 152000 Hom.: 17206 Cov.: 32 AF XY: 0.424 AC XY: 31486 AN XY: 74270

African (AFR) AF: 0.747 AC: 30971 AN: 41482

American (AMR) AF: 0.332 AC: 5062 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5162

South Asian (SAS) AF: 0.295 AC: 1423 AN: 4816

European-Finnish (FIN) AF: 0.239 AC: 2525 AN: 10550

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22095 AN: 67946

Other (OTH) AF: 0.415 AC: 877 AN: 2114

Alfa AF: 0.412 Hom.: 2941

Bravo AF: 0.451

Asia WGS AF: 0.314 AC: 1095 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	0.33
DANN	Benign	0.40
PhyloP100		-0.46
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: rs7663664; hg19: chr4-104584835;