4-103666820-C-T

Position:

• chr4-103666820-C-T

Variant summary

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

The NM_001059.3(TACR3):​c.549-8417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,012 control chromosomes in the GnomAD database, including 14,188 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 0.35 (14188 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR3	NM_001059.3	c.549-8417G>A		intron_variant		ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.549-8417G>A		intron_variant		1	NM_001059.3	ENSP00000303325	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53412 AN: 151894 Hom.: 14142 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.352 AC: 53518 AN: 152012 Hom.: 14188 Cov.: 32 AF XY: 0.350 AC XY: 26027 AN XY: 74314

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.325

Alfa AF: 0.235 Hom.: 2082

Bravo AF: 0.374

Asia WGS AF: 0.378 AC: 1316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.48

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: rs1351623; hg19: chr4-104587977;