Variant chrX-47585887-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000218388.9(TIMP1):c.453+220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,132,489 control chromosomes in the GnomAD database, including 81,322 homozygotes. There are 165,827 hemizygotes in GnomAD. 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 0.47 ( 8636 hom., 14936 hem., cov: 22)

Exomes 𝑓: 0.46 ( 72686 hom. 150891 hem. )

Consequence

TIMP1
ENST00000218388.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.904

Variant links:

Genes affected

TIMP1 (HGNC:11820): (TIMP metallopeptidase inhibitor 1) This gene belongs to the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function. Transcription of this gene is highly inducible in response to many cytokines and hormones. In addition, the expression from some but not all inactive X chromosomes suggests that this gene inactivation is polymorphic in human females. This gene is located within intron 6 of the synapsin I gene and is transcribed in the opposite direction. [provided by RefSeq, Jul 2008]

TIMP1 links:

SYN1 (HGNC:11494): (synapsin I) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

SYN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
TIMP1	NM_003254.3 linkuse as main transcript	c.453+220A>G	intron_variant	ENST00000218388.9	NP_003245.1
SYN1	NM_006950.3 linkuse as main transcript	c.775-8386T>C	intron_variant	ENST00000295987.13	NP_008881.2
SYN1	NM_133499.2 linkuse as main transcript	c.775-8386T>C	intron_variant		NP_598006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMP1	ENST00000218388.9 linkuse as main transcript	c.453+220A>G		intron_variant		1	NM_003254.3	ENSP00000218388	P1
SYN1	ENST00000295987.13 linkuse as main transcript	c.775-8386T>C		intron_variant		2	NM_006950.3	ENSP00000295987	P3	P17600-1

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

51307

AN:

109809

Hom.:

8627

Cov.:

AF XY:

0.464

AC XY:

14896

AN XY:

32099

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.372

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.460

GnomAD3 exomes

AF:

0.459

AC:

45107

AN:

98168

Hom.:

6450

AF XY:

0.466

AC XY:

16995

AN XY:

36462

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.422

Gnomad ASJ exome

AF:

0.433

Gnomad EAS exome

AF:

0.443

Gnomad SAS exome

AF:

0.529

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.435

GnomAD4 exome

AF:

0.458

AC:

468190

AN:

1022624

Hom.:

72686

Cov.:

AF XY:

0.462

AC XY:

150891

AN XY:

326844

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.428

Gnomad4 ASJ exome

AF:

0.428

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.467

AC:

51356

AN:

109865

Hom.:

8636

Cov.:

AF XY:

0.464

AC XY:

14936

AN XY:

32165

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.513

Gnomad4 FIN

AF:

0.463

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.456

Hom.:

37083

Bravo

AF:

0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.84

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over