rs11733295

Variant names:

• chr4-103661954-A-G
• rs11733295
• NM_001059.3:c.549-3551T>C

Variant summary

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

The NM_001059.3(TACR3):​c.549-3551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,248 control chromosomes in the GnomAD database, including 1,400 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 0.12 (1400 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.549-3551T>C		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.549-3551T>C		intron_variant	Intron 1 of 4	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18888 AN: 152130 Hom.: 1399 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.0761

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.124 AC: 18895 AN: 152248 Hom.: 1400 Cov.: 32 AF XY: 0.118 AC XY: 8789 AN XY: 74424

African (AFR) AF: 0.0763 AC: 3170 AN: 41566

American (AMR) AF: 0.113 AC: 1726 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.0659 AC: 341 AN: 5176

South Asian (SAS) AF: 0.0758 AC: 366 AN: 4830

European-Finnish (FIN) AF: 0.0721 AC: 765 AN: 10608

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11543 AN: 67994

Other (OTH) AF: 0.134 AC: 283 AN: 2112

Alfa AF: 0.154 Hom.: 7202

Bravo AF: 0.125

Asia WGS AF: 0.0970 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.60
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: rs11733295; hg19: chr4-104583111;