8-115649647-A-G

Variant names:

• chr8-115649647-A-G
• rs2737250
• NM_014112.5:c.-122+18898T>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+18898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,042 control chromosomes in the GnomAD database, including 21,438 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 0.49 (21438 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 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+18898T>C		intron	N/A	NP_054831.2
	TRPS1	NM_001282903.3		c.-129+18898T>C		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.10+18227T>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+18898T>C		intron	N/A	ENSP00000379065.3
	TRPS1	ENST00000220888.9	TSL:1	c.-3+18898T>C		intron	N/A	ENSP00000220888.5
	TRPS1	ENST00000519674.1	TSL:1	c.-3+18898T>C		intron	N/A	ENSP00000429174.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74652 AN: 151924 Hom.: 21381 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.492 AC: 74772 AN: 152042 Hom.: 21438 Cov.: 32 AF XY: 0.496 AC XY: 36833 AN XY: 74314

African (AFR) AF: 0.794 AC: 32954 AN: 41480

American (AMR) AF: 0.479 AC: 7320 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 917 AN: 3466

East Asian (EAS) AF: 0.369 AC: 1905 AN: 5164

South Asian (SAS) AF: 0.396 AC: 1910 AN: 4818

European-Finnish (FIN) AF: 0.484 AC: 5112 AN: 10554

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23266 AN: 67960

Other (OTH) AF: 0.418 AC: 884 AN: 2116

Alfa AF: 0.368 Hom.: 17729

Bravo AF: 0.506

Asia WGS AF: 0.428 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.82
DANN	Benign	0.24
PhyloP100		-0.24
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: rs2737250; hg19: chr8-116661874;