8-115648138-A-G

Position:

• chr8-115648138-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+20407T>C 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 151,760 control chromosomes in the GnomAD database, including 17,867 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 (17867 hom., cov: 31)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-122+20407T>C		intron_variant		ENST00000395715.8	NP_054831.2
TRPS1	NM_001282902.3	c.10+19736T>C		intron_variant			NP_001269831.1
TRPS1	NM_001282903.3	c.-129+20407T>C		intron_variant			NP_001269832.1
TRPS1	NM_001330599.2	c.-3+20407T>C		intron_variant			NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+20407T>C		intron_variant		1	NM_014112.5	ENSP00000379065	A1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69280 AN: 151642 Hom.: 17837 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.457 AC: 69364 AN: 151760 Hom.: 17867 Cov.: 31 AF XY: 0.462 AC XY: 34222 AN XY: 74144

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.393

Alfa AF: 0.338 Hom.: 18073

Bravo AF: 0.470

Asia WGS AF: 0.417 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.40

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: rs2737247; hg19: chr8-116660365;