chr8-115447173-T-C

Position:

• chr8-115447173-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014112.5(TRPS1):​c.2701-28721A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 152,322 control chromosomes in the GnomAD database, including 8 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 0.0049 (8 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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=-0.83).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00493 (751/152322) while in subpopulation SAS AF= 0.00932 (45/4826). AF 95% confidence interval is 0.00716. There are 8 homozygotes in gnomad4. There are 335 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 751 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.2701-28721A>G		intron_variant		ENST00000395715.8	NP_054831.2
TRPS1	NM_001282902.3	c.2674-28721A>G		intron_variant			NP_001269831.1
TRPS1	NM_001282903.3	c.2680-28721A>G		intron_variant			NP_001269832.1
TRPS1	NM_001330599.2	c.2662-28721A>G		intron_variant			NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.2701-28721A>G		intron_variant		1	NM_014112.5	ENSP00000379065	A1

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 754 AN: 152204 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00625

Gnomad OTH AF: 0.00955

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

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152322 Hom.: 8 Cov.: 32 AF XY: 0.00450 AC XY: 335 AN XY: 74492

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00625

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00646 Hom.: 0

Bravo AF: 0.00485

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.79

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: rs800872; hg19: chr8-116459401;