rs2737253

chr8-115651695-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TRPS1	NM_014112.5	c.-122+16850C>T		intron_variant		ENST00000395715.8
TRPS1	NM_001282902.3	c.10+16179C>T		intron_variant
TRPS1	NM_001282903.3	c.-129+16850C>T		intron_variant
TRPS1	NM_001330599.2	c.-3+16850C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+16850C>T		intron_variant		1	NM_014112.5	A1

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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.277

Alfa AF: 0.319 Hom.: 4849

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2737253; hg19: chr8-116663922; COSMIC: COSV55251836;