rs10505266

chr8-115762622-T-Cchr8-115762622-T-G

Variant summary

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

The ENST00000422939.1(TRPS1):c.-356+47011A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 152,204 control chromosomes in the GnomAD database, including 102 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 0.025 (102 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0694 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.-356+47011A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3754 AN: 152082 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0729

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.0330

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.00406

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00741

Gnomad OTH AF: 0.0267

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

GnomAD4 genome AF: 0.0247 AC: 3763 AN: 152204 Hom.: 102 Cov.: 32 AF XY: 0.0259 AC XY: 1926 AN XY: 74412

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.00406

Gnomad4 NFE AF: 0.00741

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0118 Hom.: 18

Bravo AF: 0.0315

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.31
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10505266; hg19: chr8-116774848;