rs11899823

chr2-43574573-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022065.5(THADA):c.1492T>C(p.Leu498=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,642 control chromosomes in the GnomAD database, including 87,926 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 0.33 (8715 hom., cov: 32)
  • Exomes 𝑓: 0.33 (79211 hom.)
• Consequence: THADA NM_022065.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14

Genes affected

THADA (HGNC:19217): (THADA armadillo repeat containing) This gene is the target of 2p21 choromosomal aberrations in benign thyroid adenomas. Single nucleotide polymorphisms (SNPs) in this gene may be associated with type 2 diabetes and polycystic ovary syndrome. The encoded protein is likely involved in the death receptor pathway and apoptosis. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=3.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THADA	NM_022065.5	c.1492T>C	p.Leu498=	synonymous_variant	11/38	ENST00000405975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THADA	ENST00000405975.7	c.1492T>C	p.Leu498=	synonymous_variant	11/38	1	NM_022065.5	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50788 AN: 151934 Hom.: 8698 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.310 AC: 77154 AN: 248964 Hom.: 12692 AF XY: 0.317 AC XY: 42799 AN XY: 135058

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.248

Gnomad SAS exome AF: 0.388

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.324

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.326 AC: 477086 AN: 1461590 Hom.: 79211 Cov.: 41 AF XY: 0.329 AC XY: 239184 AN XY: 727078

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.334 AC: 50841 AN: 152052 Hom.: 8715 Cov.: 32 AF XY: 0.331 AC XY: 24606 AN XY: 74312

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.314

Alfa AF: 0.334 Hom.: 15202

Bravo AF: 0.331

Asia WGS AF: 0.333 AC: 1153 AN: 3478

EpiCase AF: 0.343

EpiControl AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.0
Dann	Benign	0.79

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: rs11899823; hg19: chr2-43801712; COSMIC: COSV57679002; COSMIC: COSV57679002;