rs2737253

Variant names:

• chr8-115651695-G-A
• rs2737253
• NM_014112.5:c.-122+16850C>T

Variant summary

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

The NM_014112.5(TRPS1):​c.-122+16850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,122 control chromosomes in the GnomAD database, including 7,636 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 0.30 (7636 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-122+16850C>T		intron_variant	Intron 1 of 6	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-129+16850C>T		intron_variant	Intron 1 of 6		NP_001269832.1
TRPS1	NM_001282902.3	c.10+16179C>T		intron_variant	Intron 1 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.-3+16850C>T		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.-122+16850C>T		intron_variant	Intron 1 of 6	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45696 AN: 152004 Hom.: 7626 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.301 AC: 45721 AN: 152122 Hom.: 7636 Cov.: 32 AF XY: 0.309 AC XY: 23002 AN XY: 74376

African (AFR) AF: 0.174 AC: 7222 AN: 41530

American (AMR) AF: 0.404 AC: 6174 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 838 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1888 AN: 5172

South Asian (SAS) AF: 0.323 AC: 1553 AN: 4812

European-Finnish (FIN) AF: 0.460 AC: 4862 AN: 10574

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22129 AN: 67976

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.321 Hom.: 6877

Bravo AF: 0.295

Asia WGS AF: 0.343 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.68
PhyloP100		-1.5
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: rs2737253; hg19: chr8-116663922; COSMIC: COSV55251836;