Variant 2-232544303-G-A 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_145702.4(TIGD1):c.*3804C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,292,036 control chromosomes in the GnomAD database, including 35,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3467 hom., cov: 32)

Exomes 𝑓: 0.23 ( 32369 hom. )

Consequence

TIGD1
NM_145702.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

TIGD1 (HGNC:14523): (tigger transposable element derived 1) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

TIGD1 links:

CHRNG (HGNC:1967): (cholinergic receptor nicotinic gamma subunit) The mammalian muscle-type acetylcholine receptor is a transmembrane pentameric glycoprotein with two alpha subunits, one beta, one delta, and one epsilon (in adult skeletal muscle) or gamma (in fetal and denervated muscle) subunit. This gene, which encodes the gamma subunit, is expressed prior to the thirty-third week of gestation in humans. The gamma subunit of the acetylcholine receptor plays a role in neuromuscular organogenesis and ligand binding and disruption of gamma subunit expression prevents the correct localization of the receptor in cell membranes. Mutations in this gene cause Escobar syndrome and a lethal form of multiple pterygium syndrome. Muscle-type acetylcholine receptor is the major antigen in the autoimmune disease myasthenia gravis.[provided by RefSeq, Sep 2009]

CHRNG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-232544303-G-A is Benign according to our data. Variant chr2-232544303-G-A is described in ClinVar as [Benign]. Clinvar id is 1181421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIGD1	NM_145702.4 linkuse as main transcript	c.*3804C>T		3_prime_UTR_variant	1/1	ENST00000408957.7
CHRNG	NM_005199.5 linkuse as main transcript	c.1036-64G>A		intron_variant		ENST00000651502.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIGD1	ENST00000408957.7 linkuse as main transcript	c.*3804C>T	3_prime_UTR_variant	1/1		NM_145702.4	P1
CHRNG	ENST00000651502.1 linkuse as main transcript	c.1036-64G>A	intron_variant			NM_005199.5	P1	P07510-1
CHRNG	ENST00000389492.3 linkuse as main transcript	c.880-64G>A	intron_variant		1			P07510-2

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30919

AN:

152016

Hom.:

3468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.173

GnomAD4 exome

AF:

0.233

AC:

265482

AN:

1139902

Hom.:

32369

AF XY:

0.230

AC XY:

134152

AN XY:

582532

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.267

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.203

AC:

30928

AN:

152134

Hom.:

3467

Cov.:

AF XY:

0.204

AC XY:

15135

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.223

Hom.:

499

Bravo

AF:

0.189

Asia WGS

AF:

0.171

AC:

591

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.96

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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