rs2765

Positions:

• chr4-103589609-G-A
• chr4-103589609-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001059.3(TACR3):​c.*73C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,574,150 control chromosomes in the GnomAD database, including 317,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29952 hom., cov: 32)
  • Exomes 𝑓: 0.63 (287528 hom.)
• Consequence: TACR3 NM_001059.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.302

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-103589609-G-A is Benign according to our data. Variant chr4-103589609-G-A is described in ClinVar as [Benign]. Clinvar id is 347104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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/exons	MANE	UniProt
TACR3	NM_001059.3	c.*73C>T		3_prime_UTR_variant	5/5	ENST00000304883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACR3	ENST00000304883.3	c.*73C>T		3_prime_UTR_variant	5/5	1	NM_001059.3	P1
TACR3-AS1	ENST00000502936.1	n.190-1598G>A		intron_variant, non_coding_transcript_variant		2
TACR3-AS1	ENST00000512401.5	n.292-1598G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94849 AN: 151824 Hom.: 29928 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.632 AC: 898918 AN: 1422208 Hom.: 287528 Cov.: 24 AF XY: 0.627 AC XY: 444821 AN XY: 709524

Gnomad4 AFR exome AF: 0.588

Gnomad4 AMR exome AF: 0.682

Gnomad4 ASJ exome AF: 0.641

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.611

GnomAD4 genome AF: 0.625 AC: 94915 AN: 151942 Hom.: 29952 Cov.: 32 AF XY: 0.625 AC XY: 46398 AN XY: 74264

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.618

Alfa AF: 0.632 Hom.: 67926

Bravo AF: 0.619

Asia WGS AF: 0.475 AC: 1654 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypogonadotropic hypogonadism 11 with or without anosmia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.29

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: rs2765; hg19: chr4-104510766; COSMIC: COSV59200338;