rs10488860

Positions:

• chr4-103718517-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001059.3(TACR3):​c.548+611A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,276 control chromosomes in the GnomAD database, including 553 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 0.052 (553 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACR3	NM_001059.3	c.548+611A>T		intron_variant		ENST00000304883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACR3	ENST00000304883.3	c.548+611A>T		intron_variant		1	NM_001059.3	P1

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7822 AN: 152158 Hom.: 550 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0516 AC: 7851 AN: 152276 Hom.: 553 Cov.: 32 AF XY: 0.0501 AC XY: 3728 AN XY: 74470

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0331 Hom.: 35

Bravo AF: 0.0570

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.42
DANN	Benign	0.78

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: rs10488860; hg19: chr4-104639674;