rs4973539

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIGD1	NM_145702.4	c.1773T>C	p.Asp591Asp	synonymous_variant	1/1	ENST00000408957.7	NP_663748.1
CHRNG	NM_005199.5	c.*2394A>G		3_prime_UTR_variant	12/12	ENST00000651502.1	NP_005190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGD1	ENST00000408957.7	c.1773T>C	p.Asp591Asp	synonymous_variant	1/1	6	NM_145702.4	ENSP00000386186.3
CHRNG	ENST00000651502.1	c.*2394A>G		3_prime_UTR_variant	12/12		NM_005199.5	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

GnomAD3 exomes AF: 0.182 AC: 9534 AN: 52326 Hom.: 994 AF XY: 0.185 AC XY: 4841 AN XY: 26110

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 SAS exome AF: 0.219

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

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.193

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.191

Alfa AF: 0.198 Hom.: 4020

Bravo AF: 0.170

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs4973539; hg19: chr2-233412820;