Variant 8-115586972-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 260331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-115586972-T-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TRPS1	NM_014112.5 linkuse as main transcript	c.2700+29A>C	intron_variant	ENST00000395715.8
TRPS1	NM_001282902.3 linkuse as main transcript	c.2673+29A>C	intron_variant
TRPS1	NM_001282903.3 linkuse as main transcript	c.2679+29A>C	intron_variant
TRPS1	NM_001330599.2 linkuse as main transcript	c.2661+29A>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8 linkuse as main transcript	c.2700+29A>C		intron_variant		1	NM_014112.5	A1	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

GnomAD3 exomes

AF:

0.651

AC:

159956

AN:

245820

Hom.:

53383

AF XY:

0.643

AC XY:

86179

AN XY:

133974

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 SAS exome

AF:

0.645

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

Gnomad4 AFR exome

AF:

0.898

Gnomad4 AMR exome

AF:

0.674

Gnomad4 ASJ exome

AF:

0.584

Gnomad4 EAS exome

AF:

0.790

Gnomad4 SAS exome

AF:

0.639

Gnomad4 FIN exome

AF:

0.704

Gnomad4 NFE exome

AF:

0.570

Gnomad4 OTH exome

AF:

0.624

GnomAD4 genome

AF:

0.697

AC:

106004

AN:

152158

Hom.:

38329

Cov.:

AF XY:

0.704

AC XY:

52357

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.891

Gnomad4 AMR

AF:

0.688

Gnomad4 ASJ

AF:

0.603

Gnomad4 EAS

AF:

0.829

Gnomad4 SAS

AF:

0.663

Gnomad4 FIN

AF:

0.734

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.689

Alfa

AF:

0.596

Hom.:

32335

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

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Trichorhinophalangeal dysplasia type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Trichorhinophalangeal syndrome, type III

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.2

DANN

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over