rs10505264

Positions:

• chr8-115759255-T-C
• chr8-115759255-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+50378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,078 control chromosomes in the GnomAD database, including 8,179 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 0.18 (8179 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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 (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000422939.1	c.-356+50378A>G		intron_variant		2		ENSP00000405028

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27650 AN: 151962 Hom.: 8137 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.00649

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.183 AC: 27755 AN: 152078 Hom.: 8179 Cov.: 32 AF XY: 0.178 AC XY: 13199 AN XY: 74358

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00649

Gnomad4 OTH AF: 0.130

Alfa AF: 0.00786 Hom.: 32

Bravo AF: 0.207

Asia WGS AF: 0.0740 AC: 260 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	2.5
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: rs10505264; hg19: chr8-116771481;