rs12474030

Variant names:

• chr2-43585178-G-A
• rs12474030
• NM_022065.5:c.533+1223C>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.533+1223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,778 control chromosomes in the GnomAD database, including 2,833 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 0.17 (2833 hom., cov: 30)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.533+1223C>T		intron_variant	Intron 7 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.533+1223C>T		intron_variant	Intron 7 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25607 AN: 151660 Hom.: 2819 Cov.: 30

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00598

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.169 AC: 25662 AN: 151778 Hom.: 2833 Cov.: 30 AF XY: 0.162 AC XY: 12023 AN XY: 74182

African (AFR) AF: 0.313 AC: 12905 AN: 41288

American (AMR) AF: 0.0959 AC: 1462 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3468

East Asian (EAS) AF: 0.00600 AC: 31 AN: 5170

South Asian (SAS) AF: 0.145 AC: 697 AN: 4802

European-Finnish (FIN) AF: 0.0730 AC: 770 AN: 10542

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8900 AN: 67950

Other (OTH) AF: 0.136 AC: 286 AN: 2110

Alfa AF: 0.145 Hom.: 1037

Bravo AF: 0.173

Asia WGS AF: 0.0750 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.4
DANN	Benign	0.65
PhyloP100		-0.61
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: rs12474030; hg19: chr2-43812317;