rs2250451

Variant names:

• chr2-232544303-G-A
• rs2250451
• NM_145702.4:c.*3804C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• Publications: 3 publications found

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]

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 Gene-Disease associations (from GenCC):

• autosomal recessive multiple pterygium syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet
• CHRNG-associated hypo-akinesia disorder of prenatal onset

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• transient neonatal myasthenia gravis

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145702.4. 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
	TIGD1	NM_145702.4	MANE Select	c.*3804C>T		3_prime_UTR	Exon 1 of 1	NP_663748.1	Q96MW7
	CHRNG	NM_005199.5	MANE Select	c.1036-64G>A		intron	N/A	NP_005190.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD1	ENST00000408957.7	TSL:6 MANE Select	c.*3804C>T		3_prime_UTR	Exon 1 of 1	ENSP00000386186.3	Q96MW7
	CHRNG	ENST00000651502.1	MANE Select	c.1036-64G>A		intron	N/A	ENSP00000498757.1	P07510-1
	CHRNG	ENST00000389492.3	TSL:1	c.880-64G>A		intron	N/A	ENSP00000374143.3	P07510-2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30919 AN: 152016 Hom.: 3468 Cov.: 32

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

African (AFR) AF: 0.143 AC: 3896 AN: 27220

American (AMR) AF: 0.112 AC: 4953 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4536 AN: 24250

East Asian (EAS) AF: 0.267 AC: 10218 AN: 38258

South Asian (SAS) AF: 0.155 AC: 12308 AN: 79662

European-Finnish (FIN) AF: 0.274 AC: 12986 AN: 47398

Middle Eastern (MID) AF: 0.141 AC: 599 AN: 4254

European-Non Finnish (NFE) AF: 0.249 AC: 204990 AN: 824772

Other (OTH) AF: 0.221 AC: 10996 AN: 49756

GnomAD4 genome AF: 0.203 AC: 30928 AN: 152134 Hom.: 3467 Cov.: 32 AF XY: 0.204 AC XY: 15135 AN XY: 74346

African (AFR) AF: 0.140 AC: 5812 AN: 41516

American (AMR) AF: 0.134 AC: 2045 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1605 AN: 5164

South Asian (SAS) AF: 0.154 AC: 744 AN: 4830

European-Finnish (FIN) AF: 0.289 AC: 3045 AN: 10542

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16519 AN: 68006

Other (OTH) AF: 0.171 AC: 360 AN: 2108

Alfa AF: 0.223 Hom.: 499

Bravo AF: 0.189

Asia WGS AF: 0.171 AC: 591 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.96
DANN	Benign	0.55
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2250451; hg19: chr2-233409013; COSMIC: COSV67315698; COSMIC: COSV67315698;