rs11780385

Variant names:

• chr8-115646335-G-A
• rs11780385
• NM_014112.5:c.-122+22210C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-115646335-G-A
• chr8-115646335-G-T

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+22210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,076 control chromosomes in the GnomAD database, including 1,801 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 0.14 (1801 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.194 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.-122+22210C>T		intron	N/A	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.-129+22210C>T		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.10+21539C>T		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.-122+22210C>T		intron	N/A	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000220888.9	TSL:1	c.-3+22210C>T		intron	N/A	ENSP00000220888.5	Q9UHF7-1
	TRPS1	ENST00000519674.1	TSL:1	c.-3+22210C>T		intron	N/A	ENSP00000429174.1	E5RJ97

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20902 AN: 151958 Hom.: 1803 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.137 AC: 20895 AN: 152076 Hom.: 1801 Cov.: 32 AF XY: 0.134 AC XY: 9946 AN XY: 74344

African (AFR) AF: 0.0644 AC: 2673 AN: 41482

American (AMR) AF: 0.137 AC: 2095 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3466

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1615 AN: 10588

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13365 AN: 67944

Other (OTH) AF: 0.145 AC: 306 AN: 2106

Alfa AF: 0.152 Hom.: 678

Bravo AF: 0.134

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.59
PhyloP100		0.20
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: rs11780385; hg19: chr8-116658562;