rs727581

Variant names:

• chr8-115638264-T-C
• rs727581
• NM_014112.5:c.-121-14506A>G

Variant summary

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

The NM_014112.5(TRPS1):​c.-121-14506A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,092 control chromosomes in the GnomAD database, including 22,634 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 0.50 (22634 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-121-14506A>G		intron_variant	Intron 1 of 6	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-128-14506A>G		intron_variant	Intron 1 of 6		NP_001269832.1
TRPS1	NM_001282902.3	c.11-18204A>G		intron_variant	Intron 1 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.-2-18204A>G		intron_variant	Intron 1 of 5		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-121-14506A>G		intron_variant	Intron 1 of 6	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76036 AN: 151974 Hom.: 22577 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.501 AC: 76157 AN: 152092 Hom.: 22634 Cov.: 32 AF XY: 0.506 AC XY: 37575 AN XY: 74332

African (AFR) AF: 0.827 AC: 34302 AN: 41486

American (AMR) AF: 0.492 AC: 7521 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3466

East Asian (EAS) AF: 0.353 AC: 1826 AN: 5170

South Asian (SAS) AF: 0.451 AC: 2173 AN: 4818

European-Finnish (FIN) AF: 0.483 AC: 5102 AN: 10562

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22843 AN: 67988

Other (OTH) AF: 0.424 AC: 896 AN: 2112

Alfa AF: 0.388 Hom.: 16700

Bravo AF: 0.516

Asia WGS AF: 0.449 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.63
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs727581; hg19: chr8-116650491;