rs1526463

Variant names:

• chr8-115753005-G-A
• rs1526463
• ENST00000422939.1:c.-355-51933C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000422939.1	c.-355-51933C>T		intron_variant	Intron 1 of 4	2		ENSP00000405028.1

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

African (AFR) AF: 0.0627 AC: 2605 AN: 41518

American (AMR) AF: 0.138 AC: 2114 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 546 AN: 3466

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0462 AC: 223 AN: 4822

European-Finnish (FIN) AF: 0.167 AC: 1763 AN: 10558

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14091 AN: 67968

Other (OTH) AF: 0.152 AC: 321 AN: 2112

Alfa AF: 0.183 Hom.: 1471

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
PhyloP100		-0.80

Splicing

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

Other links and lift over

dbSNP: rs1526463; hg19: chr8-116765231;