8-115673262-T-C

Variant summary

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

The ENST00000422939.1(TRPS1):c.-219+27674A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,210 control chromosomes in the GnomAD database, including 67,991 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 0.94 (67991 hom., cov: 31)
• Consequence: TRPS1 ENST00000422939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000422939.1	c.-219+27674A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143643 AN: 152092 Hom.: 67932 Cov.: 31

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.944 AC: 143761 AN: 152210 Hom.: 67991 Cov.: 31 AF XY: 0.948 AC XY: 70554 AN XY: 74428

Gnomad4 AFR AF: 0.985

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.956

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.981

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.948

Alfa AF: 0.920 Hom.: 41292

Bravo AF: 0.947

Asia WGS AF: 0.990 AC: 3444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.7
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: rs2205256; hg19: chr8-116685489;