rs112175823

Variant names:

• chr4-103589412-A-G
• rs112175823
• NM_001059.3:c.*270T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001059.3(TACR3):​c.*270T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 396,916 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (10 hom.)
• Consequence: TACR3 NM_001059.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250
• Publications: 0 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-AS1 (HGNC:55593): (TACR3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-103589412-A-G is Benign according to our data. Variant chr4-103589412-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1204446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1887/152248) while in subpopulation AFR AF = 0.0434 (1805/41564). AF 95% confidence interval is 0.0418. There are 38 homozygotes in GnomAd4. There are 895 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.*270T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000304883.3	NP_001050.1
TACR3-AS1	NR_186501.1	n.190-1795A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.*270T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001059.3	ENSP00000303325.2
TACR3-AS1	ENST00000502936.1	n.190-1795A>G		intron_variant	Intron 2 of 4	2
TACR3-AS1	ENST00000512401.5	n.292-1795A>G		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1883 AN: 152130 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00187 AC: 457 AN: 244668 Hom.: 10 Cov.: 2 AF XY: 0.00154 AC XY: 196 AN XY: 127318

African (AFR) AF: 0.0430 AC: 366 AN: 8510

American (AMR) AF: 0.00255 AC: 26 AN: 10188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7880

East Asian (EAS) AF: 0.00 AC: 0 AN: 16740

South Asian (SAS) AF: 0.000241 AC: 6 AN: 24864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11820

Middle Eastern (MID) AF: 0.00291 AC: 3 AN: 1030

European-Non Finnish (NFE) AF: 0.000121 AC: 18 AN: 149038

Other (OTH) AF: 0.00260 AC: 38 AN: 14598

GnomAD4 genome AF: 0.0124 AC: 1887 AN: 152248 Hom.: 38 Cov.: 33 AF XY: 0.0120 AC XY: 895 AN XY: 74446

African (AFR) AF: 0.0434 AC: 1805 AN: 41564

American (AMR) AF: 0.00373 AC: 57 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68006

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.0122 Hom.: 3

Bravo AF: 0.0143

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.40
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs112175823; hg19: chr4-104510569;