rs10505265

Variant names:

• chr8-115762150-G-A
• rs10505265
• ENST00000422939.1:c.-356+47483C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-115762150-G-A
• chr8-115762150-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422939.1(TRPS1):​c.-356+47483C>T 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 152,208 control chromosomes in the GnomAD database, including 8,198 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 (8198 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 1 publications found

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]

TRPS1 Gene-Disease associations (from GenCC):

• trichorhinophalangeal syndrome type I

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• trichorhinophalangeal syndrome, type III

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• trichorhinophalangeal syndrome type I or III

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000422939.1	c.-356+47483C>T		intron_variant	Intron 1 of 4	2		ENSP00000405028.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27716 AN: 152090 Hom.: 8162 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.00653

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: 27811 AN: 152208 Hom.: 8198 Cov.: 32 AF XY: 0.178 AC XY: 13215 AN XY: 74422

African (AFR) AF: 0.620 AC: 25729 AN: 41472

American (AMR) AF: 0.0717 AC: 1096 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3472

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5172

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10616

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.00653 AC: 444 AN: 68036

Other (OTH) AF: 0.130 AC: 275 AN: 2116

Alfa AF: 0.0863 Hom.: 662

Bravo AF: 0.207

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		0.019

Splicing

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

Other links and lift over

dbSNP: rs10505265; hg19: chr8-116774376;