rs4973539

Variant names:

• chr2-232548110-A-G
• rs4973539
• NM_145702.4:c.1773T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-232548110-A-G
• chr2-232548110-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145702.4(TIGD1):​c.1773T>C​(p.Asp591Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 732,080 control chromosomes in the GnomAD database, including 14,331 homozygotes. 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 0.18 (2592 hom., cov: 33)
  • Exomes 𝑓: 0.20 (11739 hom.)
• Consequence: TIGD1 NM_145702.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 11 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: Ambry Genetics, G2P, 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: PanelApp Australia, 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.504 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 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.1773T>C	p.Asp591Asp	synonymous	Exon 1 of 1	NP_663748.1
	CHRNG	NM_005199.5	MANE Select	c.*2394A>G		3_prime_UTR	Exon 12 of 12	NP_005190.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD1	ENST00000408957.7	TSL:6 MANE Select	c.1773T>C	p.Asp591Asp	synonymous	Exon 1 of 1	ENSP00000386186.3
	CHRNG	ENST00000651502.1	MANE Select	c.*2394A>G		3_prime_UTR	Exon 12 of 12	ENSP00000498757.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26918 AN: 152146 Hom.: 2594 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.182 AC: 9534 AN: 52326 AF XY: 0.185

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.200 AC: 115754 AN: 579816 Hom.: 11739 Cov.: 8 AF XY: 0.200 AC XY: 59923 AN XY: 299622

African (AFR) AF: 0.127 AC: 1816 AN: 14314

American (AMR) AF: 0.172 AC: 2500 AN: 14522

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 3571 AN: 14744

East Asian (EAS) AF: 0.104 AC: 3103 AN: 29940

South Asian (SAS) AF: 0.213 AC: 9615 AN: 45146

European-Finnish (FIN) AF: 0.208 AC: 6450 AN: 30972

Middle Eastern (MID) AF: 0.232 AC: 895 AN: 3866

European-Non Finnish (NFE) AF: 0.207 AC: 82004 AN: 396310

Other (OTH) AF: 0.193 AC: 5800 AN: 30002

GnomAD4 genome AF: 0.177 AC: 26900 AN: 152264 Hom.: 2592 Cov.: 33 AF XY: 0.178 AC XY: 13232 AN XY: 74440

African (AFR) AF: 0.121 AC: 5012 AN: 41546

American (AMR) AF: 0.189 AC: 2887 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3472

East Asian (EAS) AF: 0.105 AC: 545 AN: 5190

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2114 AN: 10604

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13788 AN: 68018

Other (OTH) AF: 0.191 AC: 402 AN: 2110

Alfa AF: 0.196 Hom.: 5149

Bravo AF: 0.170

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.86
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4973539; hg19: chr2-233412820;