chr4-103719946-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 11 with or without anosmia

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	NM_001059.3	MANE Select	c.-271C>G		5_prime_UTR	Exon 1 of 5	NP_001050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.-271C>G		5_prime_UTR	Exon 1 of 5	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

African (AFR) AF: 0.733 AC: 8650 AN: 11800

American (AMR) AF: 0.226 AC: 3880 AN: 17196

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 2356 AN: 12664

East Asian (EAS) AF: 0.365 AC: 10417 AN: 28538

South Asian (SAS) AF: 0.335 AC: 13158 AN: 39272

European-Finnish (FIN) AF: 0.167 AC: 4385 AN: 26208

Middle Eastern (MID) AF: 0.258 AC: 467 AN: 1812

European-Non Finnish (NFE) AF: 0.160 AC: 38718 AN: 242230

Other (OTH) AF: 0.229 AC: 5447 AN: 23832

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

African (AFR) AF: 0.726 AC: 30072 AN: 41450

American (AMR) AF: 0.244 AC: 3729 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 598 AN: 3466

East Asian (EAS) AF: 0.361 AC: 1852 AN: 5134

South Asian (SAS) AF: 0.333 AC: 1604 AN: 4816

European-Finnish (FIN) AF: 0.177 AC: 1870 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10616 AN: 67950

Other (OTH) AF: 0.307 AC: 646 AN: 2102

Alfa AF: 0.116 Hom.: 271

Bravo AF: 0.356

Asia WGS AF: 0.369 AC: 1286 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.30
PhyloP100		-0.93
PromoterAI		-0.26	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3733631; hg19: chr4-104641103;