ENST00000422939.1:c.-219+27674A>G

Variant names:

• chr8-115673262-T-C
• rs2205256
• ENST00000422939.1:c.-219+27674A>G

Variant summary

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

The ENST00000422939.1(TRPS1):​c.-219+27674A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,210 control chromosomes in the GnomAD database, including 67,991 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 0.94 (67991 hom., cov: 31)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	ENST00000422939.1	TSL:2	c.-219+27674A>G		intron	N/A	ENSP00000405028.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143643 AN: 152092 Hom.: 67932 Cov.: 31

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.944 AC: 143761 AN: 152210 Hom.: 67991 Cov.: 31 AF XY: 0.948 AC XY: 70554 AN XY: 74428

African (AFR) AF: 0.985 AC: 40924 AN: 41556

American (AMR) AF: 0.961 AC: 14686 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3317 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5173 AN: 5174

South Asian (SAS) AF: 0.981 AC: 4737 AN: 4830

European-Finnish (FIN) AF: 0.938 AC: 9933 AN: 10590

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61911 AN: 67988

Other (OTH) AF: 0.948 AC: 2002 AN: 2112

Alfa AF: 0.924 Hom.: 83549

Bravo AF: 0.947

Asia WGS AF: 0.990 AC: 3444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.77
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs2205256; hg19: chr8-116685489;