rs7590268

chr2-43312986-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022065.5(THADA):c.4438+7460A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,034 control chromosomes in the GnomAD database, including 3,586 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 0.21 (3586 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THADA	NM_022065.5	c.4438+7460A>C		intron_variant		ENST00000405975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THADA	ENST00000405975.7	c.4438+7460A>C		intron_variant		1	NM_022065.5	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32478 AN: 151916 Hom.: 3582 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.214 AC: 32488 AN: 152034 Hom.: 3586 Cov.: 32 AF XY: 0.213 AC XY: 15852 AN XY: 74288

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.221

Alfa AF: 0.238 Hom.: 3376

Bravo AF: 0.204

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	15
Dann	Benign	0.82

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: rs7590268; hg19: chr2-43540125;