rs7559891

Variant names:

• chr2-43539900-G-A
• rs7559891
• NM_022065.5:c.3264+1259C>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.3264+1259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,894 control chromosomes in the GnomAD database, including 28,160 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 0.60 (28160 hom., cov: 31)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.3264+1259C>T		intron_variant	Intron 21 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.3264+1259C>T		intron_variant	Intron 21 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90431 AN: 151776 Hom.: 28121 Cov.: 31

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.596 AC: 90528 AN: 151894 Hom.: 28160 Cov.: 31 AF XY: 0.588 AC XY: 43666 AN XY: 74214

African (AFR) AF: 0.752 AC: 31178 AN: 41436

American (AMR) AF: 0.430 AC: 6556 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2223 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5170

South Asian (SAS) AF: 0.640 AC: 3087 AN: 4822

European-Finnish (FIN) AF: 0.515 AC: 5413 AN: 10514

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.571 AC: 38820 AN: 67932

Other (OTH) AF: 0.569 AC: 1199 AN: 2108

Alfa AF: 0.571 Hom.: 12236

Bravo AF: 0.593

Asia WGS AF: 0.488 AC: 1693 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.46
PhyloP100		-0.014
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: rs7559891; hg19: chr2-43767039;