4-103620984-A-C

Variant names:

• chr4-103620984-A-C
• rs13134657
• NM_001059.3:c.889-29301T>G

Variant summary

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

The NM_001059.3(TACR3):​c.889-29301T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,262 control chromosomes in the GnomAD database, including 1,482 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 0.13 (1482 hom., cov: 33)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.889-29301T>G		intron_variant	Intron 3 of 4	ENST00000304883.3	NP_001050.1
TACR3-AS1	NR_186501.1	n.572-3297A>C		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.889-29301T>G		intron_variant	Intron 3 of 4	1	NM_001059.3	ENSP00000303325.2
TACR3-AS1	ENST00000502936.1	n.572-3297A>C		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19945 AN: 152144 Hom.: 1474 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.131 AC: 19972 AN: 152262 Hom.: 1482 Cov.: 33 AF XY: 0.129 AC XY: 9639 AN XY: 74446

African (AFR) AF: 0.184 AC: 7625 AN: 41548

American (AMR) AF: 0.135 AC: 2065 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3468

East Asian (EAS) AF: 0.0428 AC: 222 AN: 5186

South Asian (SAS) AF: 0.168 AC: 809 AN: 4824

European-Finnish (FIN) AF: 0.0734 AC: 779 AN: 10612

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7643 AN: 68010

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.117 Hom.: 207

Bravo AF: 0.139

Asia WGS AF: 0.151 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		1.3
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: rs13134657; hg19: chr4-104542141;