NM_022065.5:c.4438+7460A>C

Variant names:

• chr2-43312986-T-G
• rs7590268
• NM_022065.5:c.4438+7460A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 51 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022065.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	NM_022065.5	MANE Select	c.4438+7460A>C		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.4438+7460A>C		intron	N/A	NP_001077422.1	Q6YHU6-1
	THADA	NM_001345925.2		c.4438+7460A>C		intron	N/A	NP_001332854.1	Q6YHU6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.4438+7460A>C		intron	N/A	ENSP00000386088.2	Q6YHU6-1
	THADA	ENST00000405006.8	TSL:1	c.4438+7460A>C		intron	N/A	ENSP00000385995.4	Q6YHU6-1
	THADA	ENST00000855634.1		c.4438+7460A>C		intron	N/A	ENSP00000525693.1

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

African (AFR) AF: 0.194 AC: 8039 AN: 41478

American (AMR) AF: 0.167 AC: 2552 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3468

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5178

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4826

European-Finnish (FIN) AF: 0.262 AC: 2762 AN: 10538

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16327 AN: 67944

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.228 Hom.: 9599

Bravo AF: 0.204

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		1.3
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: rs7590268; hg19: chr2-43540125;