rs1526463

chr8-115753005-G-A

Variant summary

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

The ENST00000422939.1(TRPS1):c.-355-51933C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,114 control chromosomes in the GnomAD database, including 1,960 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 0.14 (1960 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

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]

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 (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000422939.1	c.-355-51933C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21802 AN: 151996 Hom.: 1961 Cov.: 32

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.143 AC: 21800 AN: 152114 Hom.: 1960 Cov.: 32 AF XY: 0.140 AC XY: 10371 AN XY: 74340

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.152

Alfa AF: 0.182 Hom.: 1292

Bravo AF: 0.138

Asia WGS AF: 0.0250 AC: 90 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	0.85
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1526463; hg19: chr8-116765231;