rs720928

Variant names:

• chr8-115685649-A-G
• rs720928
• ENST00000422939.1:c.-219+15287T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-115685649-A-G
• chr8-115685649-A-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+15287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,986 control chromosomes in the GnomAD database, including 36,925 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 0.69 (36925 hom., cov: 33)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.763 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.-219+15287T>C		intron_variant	Intron 2 of 4	2		ENSP00000405028.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104631 AN: 151868 Hom.: 36933 Cov.: 33

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.689 AC: 104646 AN: 151986 Hom.: 36925 Cov.: 33 AF XY: 0.687 AC XY: 51013 AN XY: 74276

African (AFR) AF: 0.523 AC: 21718 AN: 41488

American (AMR) AF: 0.714 AC: 10881 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2897 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3278 AN: 5144

South Asian (SAS) AF: 0.784 AC: 3780 AN: 4824

European-Finnish (FIN) AF: 0.722 AC: 7616 AN: 10550

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52034 AN: 67952

Other (OTH) AF: 0.724 AC: 1524 AN: 2106

Alfa AF: 0.718 Hom.: 4703

Bravo AF: 0.683

Asia WGS AF: 0.683 AC: 2372 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs720928; hg19: chr8-116697876;