rs12468394

Variant names:

• chr2-43334022-C-A
• rs12468394
• NM_022065.5:c.4343+10100G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):​c.4343+10100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,068 control chromosomes in the GnomAD database, including 17,643 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 0.48 (17643 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 21 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.4343+10100G>T		intron_variant	Intron 30 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.4343+10100G>T		intron_variant	Intron 30 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72539 AN: 151950 Hom.: 17629 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.467

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72591 AN: 152068 Hom.: 17643 Cov.: 32 AF XY: 0.479 AC XY: 35633 AN XY: 74320

African (AFR) AF: 0.472 AC: 19563 AN: 41474

American (AMR) AF: 0.366 AC: 5591 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1392 AN: 5178

South Asian (SAS) AF: 0.632 AC: 3043 AN: 4814

European-Finnish (FIN) AF: 0.534 AC: 5644 AN: 10564

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.498 AC: 33829 AN: 67978

Other (OTH) AF: 0.468 AC: 989 AN: 2114

Alfa AF: 0.486 Hom.: 37272

Bravo AF: 0.459

Asia WGS AF: 0.452 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		0.20
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: rs12468394; hg19: chr2-43561161;