rs11899823

Variant names:

• chr2-43574573-A-G
• rs11899823
• NM_022065.5:c.1492T>C

Variant summary

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

The NM_022065.5(THADA):​c.1492T>C​(p.Leu498Leu) 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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022065.5. 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
	THADA	NM_022065.5	MANE Select	c.1492T>C	p.Leu498Leu	synonymous	Exon 11 of 38	NP_071348.3
	THADA	NM_001083953.2		c.1492T>C	p.Leu498Leu	synonymous	Exon 11 of 38	NP_001077422.1	Q6YHU6-1
	THADA	NM_001345925.2		c.1492T>C	p.Leu498Leu	synonymous	Exon 12 of 39	NP_001332854.1	Q6YHU6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.1492T>C	p.Leu498Leu	synonymous	Exon 11 of 38	ENSP00000386088.2	Q6YHU6-1
	THADA	ENST00000405006.8	TSL:1	c.1492T>C	p.Leu498Leu	synonymous	Exon 11 of 38	ENSP00000385995.4	Q6YHU6-1
	THADA	ENST00000404790.5	TSL:1	c.1492T>C	p.Leu498Leu	synonymous	Exon 11 of 17	ENSP00000384266.1	Q6YHU6-6

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

GnomAD2 exomes AF: 0.310 AC: 77154 AN: 248964 AF XY: 0.317

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 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

African (AFR) AF: 0.386 AC: 12911 AN: 33478

American (AMR) AF: 0.175 AC: 7814 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 10202 AN: 26134

East Asian (EAS) AF: 0.283 AC: 11210 AN: 39680

South Asian (SAS) AF: 0.382 AC: 32982 AN: 86252

European-Finnish (FIN) AF: 0.299 AC: 15959 AN: 53372

Middle Eastern (MID) AF: 0.368 AC: 2123 AN: 5768

European-Non Finnish (NFE) AF: 0.327 AC: 364048 AN: 1111812

Other (OTH) AF: 0.329 AC: 19837 AN: 60374

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

African (AFR) AF: 0.388 AC: 16104 AN: 41468

American (AMR) AF: 0.238 AC: 3639 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5166

South Asian (SAS) AF: 0.390 AC: 1878 AN: 4816

European-Finnish (FIN) AF: 0.309 AC: 3270 AN: 10574

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22186 AN: 67968

Other (OTH) AF: 0.314 AC: 665 AN: 2116

Alfa AF: 0.332 Hom.: 19820

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.0
DANN	Benign	0.79
PhyloP100		3.1
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: rs11899823; hg19: chr2-43801712; COSMIC: COSV57679002; COSMIC: COSV57679002;