rs800586

Variant names:

• chr8-115801679-G-A
• rs800586
• ENST00000422939.1:c.-356+7954C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-115801679-G-A
• chr8-115801679-G-C
• chr8-115801679-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+7954C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,432 control chromosomes in the GnomAD database, including 27,558 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 0.55 (27558 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 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+7954C>T		intron_variant	Intron 1 of 4	2		ENSP00000405028.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83005 AN: 151314 Hom.: 27567 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.548 AC: 82984 AN: 151432 Hom.: 27558 Cov.: 32 AF XY: 0.545 AC XY: 40308 AN XY: 73988

African (AFR) AF: 0.174 AC: 7205 AN: 41400

American (AMR) AF: 0.465 AC: 7051 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2780 AN: 3450

East Asian (EAS) AF: 0.532 AC: 2725 AN: 5120

South Asian (SAS) AF: 0.684 AC: 3300 AN: 4822

European-Finnish (FIN) AF: 0.700 AC: 7398 AN: 10564

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50347 AN: 67602

Other (OTH) AF: 0.622 AC: 1307 AN: 2100

Alfa AF: 0.653 Hom.: 82312

Bravo AF: 0.516

Asia WGS AF: 0.558 AC: 1934 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		0.042

Splicing

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

Other links and lift over

dbSNP: rs800586; hg19: chr8-116813905;