chr8-115636338-A-C

Variant names:

• chr8-115636338-A-C
• rs2737229
• NM_014112.5:c.-121-12580T>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.-121-12580T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,034 control chromosomes in the GnomAD database, including 20,995 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 0.47 (20995 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652
• Publications: 41 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014112.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	NM_014112.5	MANE Select	c.-121-12580T>G		intron	N/A	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.-128-12580T>G		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.11-16278T>G		intron	N/A	NP_001269831.1	Q9UHF7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	ENST00000395715.8	TSL:1 MANE Select	c.-121-12580T>G		intron	N/A	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000220888.9	TSL:1	c.-2-16278T>G		intron	N/A	ENSP00000220888.5	Q9UHF7-1
	TRPS1	ENST00000519674.1	TSL:1	c.-2-16278T>G		intron	N/A	ENSP00000429174.1	E5RJ97

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71392 AN: 151916 Hom.: 20932 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.470 AC: 71523 AN: 152034 Hom.: 20995 Cov.: 32 AF XY: 0.474 AC XY: 35207 AN XY: 74290

African (AFR) AF: 0.828 AC: 34361 AN: 41494

American (AMR) AF: 0.467 AC: 7133 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1890 AN: 5160

South Asian (SAS) AF: 0.399 AC: 1921 AN: 4810

European-Finnish (FIN) AF: 0.401 AC: 4228 AN: 10540

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19951 AN: 67982

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.335 Hom.: 30157

Bravo AF: 0.492

Asia WGS AF: 0.434 AC: 1513 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		0.65
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: rs2737229; hg19: chr8-116648565;