dbSNP rs11899823: THADA:p.Leu498Leu (chr2-43574573-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.14

Publications

24 publications found

Variant links:

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]

THADA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5 link	c.1492T>C	p.Leu498Leu	synonymous_variant	Exon 11 of 38	ENST00000405975.7	NP_071348.3	Q6YHU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7 link	c.1492T>C	p.Leu498Leu	synonymous_variant	Exon 11 of 38	1	NM_022065.5	ENSP00000386088.2		Q6YHU6-1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50788

AN:

151934

Hom.:

8698

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.329

AC XY:

239184

AN XY:

727078

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19122

38244

57365

76487

95609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.334

AC:

50841

AN:

152052

Hom.:

8715

Cov.:

AF XY:

0.331

AC XY:

24606

AN XY:

74312

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1723

3445

5168

6890

8613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.0

(source)

DANN

Benign

0.79

PhyloP100

3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs11899823

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over