rs2765

Variant names:

• chr4-103589609-G-A
• rs2765
• NM_001059.3:c.*73C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	NM_001059.3	MANE Select	c.*73C>T		3_prime_UTR	Exon 5 of 5	NP_001050.1	P29371
	TACR3-AS1	NR_186501.1		n.190-1598G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.*73C>T		3_prime_UTR	Exon 5 of 5	ENSP00000303325.2	P29371
	TACR3-AS1	ENST00000502936.1	TSL:2	n.190-1598G>A		intron	N/A
	TACR3-AS1	ENST00000512401.5	TSL:2	n.292-1598G>A		intron	N/A

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

African (AFR) AF: 0.588 AC: 19182 AN: 32620

American (AMR) AF: 0.682 AC: 30358 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 16572 AN: 25834

East Asian (EAS) AF: 0.477 AC: 18746 AN: 39286

South Asian (SAS) AF: 0.449 AC: 38180 AN: 85038

European-Finnish (FIN) AF: 0.747 AC: 38323 AN: 51326

Middle Eastern (MID) AF: 0.573 AC: 3207 AN: 5598

European-Non Finnish (NFE) AF: 0.647 AC: 698315 AN: 1079054

Other (OTH) AF: 0.611 AC: 36035 AN: 58962

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

African (AFR) AF: 0.592 AC: 24525 AN: 41414

American (AMR) AF: 0.625 AC: 9541 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2434 AN: 5158

South Asian (SAS) AF: 0.439 AC: 2111 AN: 4814

European-Finnish (FIN) AF: 0.758 AC: 7997 AN: 10548

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43914 AN: 67968

Other (OTH) AF: 0.618 AC: 1300 AN: 2104

Alfa AF: 0.632 Hom.: 103817

Bravo AF: 0.619

Asia WGS AF: 0.475 AC: 1654 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypogonadotropic hypogonadism 11 with or without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.29
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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