8-115621472-C-T

Variant names:

• chr8-115621472-C-T
• rs2721937
• NM_014112.5:c.38-1412G>A

Variant summary

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

The NM_014112.5(TRPS1):​c.38-1412G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,216 control chromosomes in the GnomAD database, including 2,611 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 0.16 (2611 hom., cov: 33)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 12 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 (EAS) allele frequency at 95% confidence interval = 0.302 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	NM_014112.5	MANE Select	c.38-1412G>A		intron	N/A	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.17-1412G>A		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.11-1412G>A		intron	N/A	NP_001269831.1	Q9UHF7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	ENST00000395715.8	TSL:1 MANE Select	c.38-1412G>A		intron	N/A	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000220888.9	TSL:1	c.-2-1412G>A		intron	N/A	ENSP00000220888.5	Q9UHF7-1
	TRPS1	ENST00000519674.1	TSL:1	c.-2-1412G>A		intron	N/A	ENSP00000429174.1	E5RJ97

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24335 AN: 152098 Hom.: 2605 Cov.: 33

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.160 AC: 24346 AN: 152216 Hom.: 2611 Cov.: 33 AF XY: 0.167 AC XY: 12428 AN XY: 74406

African (AFR) AF: 0.0431 AC: 1790 AN: 41552

American (AMR) AF: 0.238 AC: 3650 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1630 AN: 5178

South Asian (SAS) AF: 0.165 AC: 798 AN: 4824

European-Finnish (FIN) AF: 0.302 AC: 3194 AN: 10568

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12482 AN: 68002

Other (OTH) AF: 0.144 AC: 303 AN: 2110

Alfa AF: 0.165 Hom.: 5269

Bravo AF: 0.154

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.031
DANN	Benign	0.17
PhyloP100		-1.4
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: rs2721937; hg19: chr8-116633699;