rs4794068

Positions:

• chr17-49844979-G-A

Variant summary

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

The NM_001077506.2(TAC4):​c.106-822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,152 control chromosomes in the GnomAD database, including 4,605 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 0.23 (4605 hom., cov: 32)
• Consequence: TAC4 NM_001077506.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

TAC4 (HGNC:16641): (tachykinin precursor 4) This gene is a member of the tachykinin family of neurotransmitter-encoding genes. Tachykinin proteins are cleaved into small, secreted peptides that activate members of a family of receptor proteins. The products of this gene preferentially activate tachykinin receptor 1, and are thought to regulate peripheral endocrine and paracrine functions including blood pressure, the immune system, and endocrine gland secretion. The products of this gene lack a dibasic cleavage site found in other tachykinin proteins. Consequently, the nature of the cleavage products generated in vivo remains to be determined. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAC4	NM_001077506.2	c.106-822C>T		intron_variant		ENST00000436235.6	NP_001070974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAC4	ENST00000436235.6	c.106-822C>T		intron_variant		1	NM_001077506.2	ENSP00000399702	A2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35468 AN: 152034 Hom.: 4591 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.233 AC: 35506 AN: 152152 Hom.: 4605 Cov.: 32 AF XY: 0.238 AC XY: 17689 AN XY: 74364

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.205

Alfa AF: 0.176 Hom.: 3400

Bravo AF: 0.233

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	14
DANN	Benign	0.50

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: rs4794068; hg19: chr17-47922341;