rs2737250

Positions:

• chr8-115649647-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014112.5(TRPS1):​c.-122+18898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,042 control chromosomes in the GnomAD database, including 21,438 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 0.49 (21438 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-122+18898T>C		intron_variant		ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-129+18898T>C		intron_variant			NP_001269832.1
TRPS1	NM_001282902.3	c.10+18227T>C		intron_variant			NP_001269831.1
TRPS1	NM_001330599.2	c.-3+18898T>C		intron_variant			NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+18898T>C		intron_variant		1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74652 AN: 151924 Hom.: 21381 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.492 AC: 74772 AN: 152042 Hom.: 21438 Cov.: 32 AF XY: 0.496 AC XY: 36833 AN XY: 74314

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.418

Alfa AF: 0.378 Hom.: 5647

Bravo AF: 0.506

Asia WGS AF: 0.428 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.82
DANN	Benign	0.24

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: rs2737250; hg19: chr8-116661874;