rs179442

chr8-115657542-C-T

Variant summary

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

The NM_014112.5(TRPS1):c.-122+11003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,814 control chromosomes in the GnomAD database, including 17,920 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 0.46 (17920 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPS1	NM_014112.5	c.-122+11003G>A		intron_variant		ENST00000395715.8
TRPS1	NM_001282902.3	c.10+10332G>A		intron_variant
TRPS1	NM_001282903.3	c.-129+11003G>A		intron_variant
TRPS1	NM_001330599.2	c.-3+11003G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+11003G>A		intron_variant		1	NM_014112.5	A1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69332 AN: 151694 Hom.: 17888 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.457 AC: 69422 AN: 151814 Hom.: 17920 Cov.: 32 AF XY: 0.462 AC XY: 34240 AN XY: 74186

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.397

Alfa AF: 0.414 Hom.: 2733

Bravo AF: 0.471

Asia WGS AF: 0.418 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.3
Dann	Benign	0.52

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: rs179442; hg19: chr8-116669769;