rs12478601

Positions:

• chr2-43494369-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):​c.3744+4464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,008 control chromosomes in the GnomAD database, including 29,098 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 0.61 (29098 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5	c.3744+4464G>A		intron_variant		ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.3744+4464G>A		intron_variant		1	NM_022065.5	ENSP00000386088	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91895 AN: 151890 Hom.: 29057 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.605 AC: 91995 AN: 152008 Hom.: 29098 Cov.: 32 AF XY: 0.598 AC XY: 44392 AN XY: 74268

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.577

Alfa AF: 0.575 Hom.: 59514

Bravo AF: 0.601

Asia WGS AF: 0.496 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.42

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: rs12478601; hg19: chr2-43721508;