chr8-115648138-A-G

Variant names:

• chr8-115648138-A-G
• rs2737247
• NM_014112.5:c.-122+20407T>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+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
• Publications: 10 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=-0.82).
• 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 rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-122+20407T>C		intron_variant	Intron 1 of 6	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-129+20407T>C		intron_variant	Intron 1 of 6		NP_001269832.1
TRPS1	NM_001282902.3	c.10+19736T>C		intron_variant	Intron 1 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.-3+20407T>C		intron_variant	Intron 1 of 5		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+20407T>C		intron_variant	Intron 1 of 6	1	NM_014112.5	ENSP00000379065.3

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

African (AFR) AF: 0.694 AC: 28660 AN: 41324

American (AMR) AF: 0.480 AC: 7327 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3468

East Asian (EAS) AF: 0.368 AC: 1890 AN: 5132

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4818

European-Finnish (FIN) AF: 0.460 AC: 4832 AN: 10506

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22541 AN: 67940

Other (OTH) AF: 0.393 AC: 828 AN: 2106

Alfa AF: 0.362 Hom.: 45656

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
PhyloP100		-0.98
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: rs2737247; hg19: chr8-116660365;