chr8-115586972-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014112.5(TRPS1):c.2700+29A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,613,052 control chromosomes in the GnomAD database, including 303,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38329 hom., cov: 33)

Exomes 𝑓: 0.60 ( 265456 hom. )

Consequence

TRPS1
NM_014112.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.57

Publications

106 publications found

Variant links:

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

TRPS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 8-115586972-T-G is Benign according to our data. Variant chr8-115586972-T-G is described in ClinVar as Benign. ClinVar VariationId is 260331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5 link	c.2700+29A>C	intron_variant	Intron 5 of 6	ENST00000395715.8	NP_054831.2	Q9UHF7-2
TRPS1	NM_001282903.3 link	c.2679+29A>C	intron_variant	Intron 5 of 6		NP_001269832.1	Q9UHF7
TRPS1	NM_001282902.3 link	c.2673+29A>C	intron_variant	Intron 4 of 5		NP_001269831.1	Q9UHF7-3
TRPS1	NM_001330599.2 link	c.2661+29A>C	intron_variant	Intron 4 of 5		NP_001317528.1	Q9UHF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8 link	c.2700+29A>C		intron_variant	Intron 5 of 6	1	NM_014112.5	ENSP00000379065.3		Q9UHF7-2

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105889

AN:

152040

Hom.:

38266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.643

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.683

GnomAD2 exomes

AF:

0.651

AC:

159956

AN:

245820

AF XY:

0.643

show subpopulations

Gnomad AFR exome

AF:

0.897

Gnomad AMR exome

AF:

0.671

Gnomad ASJ exome

AF:

0.588

Gnomad EAS exome

AF:

0.838

Gnomad FIN exome

AF:

0.715

Gnomad NFE exome

AF:

0.577

Gnomad OTH exome

AF:

0.630

GnomAD4 exome

AF:

0.598

AC:

874033

AN:

1460894

Hom.:

265456

Cov.:

AF XY:

0.598

AC XY:

434856

AN XY:

726778

show subpopulations

African (AFR)

AF:

0.898

AC:

30070

AN:

33468

American (AMR)

AF:

0.674

AC:

30158

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.584

AC:

15253

AN:

26136

East Asian (EAS)

AF:

0.790

AC:

31363

AN:

39688

South Asian (SAS)

AF:

0.639

AC:

55126

AN:

86204

European-Finnish (FIN)

AF:

0.704

AC:

37221

AN:

52838

Middle Eastern (MID)

AF:

0.650

AC:

3664

AN:

5640

European-Non Finnish (NFE)

AF:

0.570

AC:

633497

AN:

1111830

Other (OTH)

AF:

0.624

AC:

37681

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

19520

39040

58559

78079

97599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17786

35572

53358

71144

88930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.697

AC:

106004

AN:

152158

Hom.:

38329

Cov.:

AF XY:

0.704

AC XY:

52357

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.891

AC:

37002

AN:

41544

American (AMR)

AF:

0.688

AC:

10507

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

2093

AN:

3470

East Asian (EAS)

AF:

0.829

AC:

4275

AN:

5158

South Asian (SAS)

AF:

0.663

AC:

3193

AN:

4818

European-Finnish (FIN)

AF:

0.734

AC:

7776

AN:

10596

Middle Eastern (MID)

AF:

0.634

AC:

185

AN:

292

European-Non Finnish (NFE)

AF:

0.575

AC:

39083

AN:

67984

Other (OTH)

AF:

0.689

AC:

1453

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1557

3114

4672

6229

7786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.614

Hom.:

89121

Bravo

AF:

0.703

Asia WGS

AF:

0.760

AC:

2641

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Trichorhinophalangeal dysplasia type I

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Trichorhinophalangeal syndrome, type III

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.2

(source)

DANN

Benign

0.66

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over