chr4-103719946-G-C

Variant names:

• chr4-103719946-G-C
• rs3733631
• NM_001059.3:c.-271C>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001059.3(TACR3):​c.-271C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 555,554 control chromosomes in the GnomAD database, including 25,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (13257 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12287 hom.)
• Consequence: TACR3 NM_001059.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.932

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-103719946-G-C is Benign according to our data. Variant chr4-103719946-G-C is described in ClinVar as [Benign]. Clinvar id is 672984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.-271C>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.-271C>G		5_prime_UTR_variant	Exon 1 of 5	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51128 AN: 151884 Hom.: 13215 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.217 AC: 87478 AN: 403552 Hom.: 12287 AF XY: 0.221 AC XY: 46491 AN XY: 210590

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.337 AC: 51227 AN: 152002 Hom.: 13257 Cov.: 32 AF XY: 0.336 AC XY: 24997 AN XY: 74312

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.307

Alfa AF: 0.116 Hom.: 271

Bravo AF: 0.356

Asia WGS AF: 0.369 AC: 1286 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3733631; hg19: chr4-104641103;