8-115621472-C-T

Position:

• chr8-115621472-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.38-1412G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,216 control chromosomes in the GnomAD database, including 2,611 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 0.16 (2611 hom., cov: 33)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPS1	NM_014112.5	c.38-1412G>A		intron_variant		ENST00000395715.8
TRPS1	NM_001282902.3	c.11-1412G>A		intron_variant
TRPS1	NM_001282903.3	c.17-1412G>A		intron_variant
TRPS1	NM_001330599.2	c.-2-1412G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8	c.38-1412G>A		intron_variant		1	NM_014112.5	A1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24335 AN: 152098 Hom.: 2605 Cov.: 33

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.160 AC: 24346 AN: 152216 Hom.: 2611 Cov.: 33 AF XY: 0.167 AC XY: 12428 AN XY: 74406

Gnomad4 AFR AF: 0.0431

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.144

Alfa AF: 0.166 Hom.: 2880

Bravo AF: 0.154

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.031
DANN	Benign	0.17

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: rs2721937; hg19: chr8-116633699;