rs2178951

Variant names:

• chr8-115647307-A-G
• rs2178951
• NM_014112.5:c.-122+21238T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014112.5(TRPS1):​c.-122+21238T>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 151,962 control chromosomes in the GnomAD database, including 17,875 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 (17875 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 6 publications found

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]

TRPS1 Gene-Disease associations (from GenCC):

• trichorhinophalangeal syndrome type I

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• trichorhinophalangeal syndrome, type III

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• trichorhinophalangeal syndrome type I or III

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014112.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	NM_014112.5	MANE Select	c.-122+21238T>C		intron	N/A	NP_054831.2
	TRPS1	NM_001282903.3		c.-129+21238T>C		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.10+20567T>C		intron	N/A	NP_001269831.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	ENST00000395715.8	TSL:1 MANE Select	c.-122+21238T>C		intron	N/A	ENSP00000379065.3
	TRPS1	ENST00000220888.9	TSL:1	c.-3+21238T>C		intron	N/A	ENSP00000220888.5
	TRPS1	ENST00000519674.1	TSL:1	c.-3+21238T>C		intron	N/A	ENSP00000429174.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69330 AN: 151844 Hom.: 17845 Cov.: 32

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.330

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: 69414 AN: 151962 Hom.: 17875 Cov.: 32 AF XY: 0.461 AC XY: 34265 AN XY: 74252

African (AFR) AF: 0.693 AC: 28703 AN: 41432

American (AMR) AF: 0.480 AC: 7336 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1895 AN: 5166

South Asian (SAS) AF: 0.399 AC: 1923 AN: 4824

European-Finnish (FIN) AF: 0.461 AC: 4851 AN: 10532

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.330 AC: 22448 AN: 67934

Other (OTH) AF: 0.393 AC: 830 AN: 2112

Alfa AF: 0.401 Hom.: 2239

Bravo AF: 0.470

Asia WGS AF: 0.415 AC: 1441 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.71
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2178951; hg19: chr8-116659534;