rs179456

Positions:

• chr8-115682885-G-A

Variant summary

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

The ENST00000422939.1(TRPS1):​c.-219+18051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,078 control chromosomes in the GnomAD database, including 3,569 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 0.21 (3569 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

Genes affected

TRPS1 (HGNC:12340): (transcriptional repressor GATA binding 1) This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.115682885G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000422939.1	c.-219+18051C>T		intron_variant		2		ENSP00000405028.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31407 AN: 151960 Hom.: 3562 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.207 AC: 31434 AN: 152078 Hom.: 3569 Cov.: 32 AF XY: 0.210 AC XY: 15626 AN XY: 74350

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.193

Alfa AF: 0.221 Hom.: 5237

Bravo AF: 0.199

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs179456; hg19: chr8-116695112;