chr8-115708836-C-T

Position:

• chr8-115708836-C-T

Variant summary

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

The ENST00000422939.1(TRPS1):​c.-355-7764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 152,160 control chromosomes in the GnomAD database, including 156 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 0.031 (156 hom., cov: 32)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000422939.1	c.-355-7764G>A		intron_variant		2		ENSP00000405028

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4765 AN: 152040 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.00406

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00625

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0314 AC: 4773 AN: 152160 Hom.: 156 Cov.: 32 AF XY: 0.0324 AC XY: 2409 AN XY: 74398

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.0736

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.0308

Gnomad4 SAS AF: 0.0380

Gnomad4 FIN AF: 0.00406

Gnomad4 NFE AF: 0.00625

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0119 Hom.: 25

Bravo AF: 0.0396

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10505263; hg19: chr8-116721063;