rs179456

Variant names:

• chr8-115682885-G-A
• rs179456
• ENST00000422939.1:c.-219+18051C>T

Variant summary

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

The ENST00000422939.1(TRPS1):​c.-219+18051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,078 control chromosomes in the GnomAD database, including 3,569 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 0.21 (3569 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422939.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	ENST00000422939.1	TSL:2	c.-219+18051C>T		intron	N/A	ENSP00000405028.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31407 AN: 151960 Hom.: 3562 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.207 AC: 31434 AN: 152078 Hom.: 3569 Cov.: 32 AF XY: 0.210 AC XY: 15626 AN XY: 74350

African (AFR) AF: 0.125 AC: 5172 AN: 41518

American (AMR) AF: 0.241 AC: 3674 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3468

East Asian (EAS) AF: 0.360 AC: 1855 AN: 5148

South Asian (SAS) AF: 0.192 AC: 922 AN: 4812

European-Finnish (FIN) AF: 0.277 AC: 2932 AN: 10570

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15682 AN: 67976

Other (OTH) AF: 0.193 AC: 407 AN: 2112

Alfa AF: 0.219 Hom.: 6502

Bravo AF: 0.199

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.35
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs179456; hg19: chr8-116695112;