4-103635509-A-G

Position:

• chr4-103635509-A-G

Variant summary

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

The NM_001059.3(TACR3):​c.888+20685T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,812 control chromosomes in the GnomAD database, including 17,219 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 0.43 (17219 hom., cov: 31)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR3	NM_001059.3	c.888+20685T>C		intron_variant		ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.888+20685T>C		intron_variant		1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65821 AN: 151692 Hom.: 17178 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.434 AC: 65909 AN: 151812 Hom.: 17219 Cov.: 31 AF XY: 0.425 AC XY: 31557 AN XY: 74184

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.409

Alfa AF: 0.329 Hom.: 11348

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.24

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: rs3796969; hg19: chr4-104556666;