rs7595299

Variant names:

• chr2-43253178-G-A
• rs7595299
• NM_022065.5:c.5297-20296C>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.5297-20296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,120 control chromosomes in the GnomAD database, including 1,778 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 0.15 (1778 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.5297-20296C>T		intron_variant	Intron 36 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.5297-20296C>T		intron_variant	Intron 36 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22714 AN: 152002 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.149 AC: 22731 AN: 152120 Hom.: 1778 Cov.: 32 AF XY: 0.153 AC XY: 11382 AN XY: 74390

African (AFR) AF: 0.121 AC: 5002 AN: 41500

American (AMR) AF: 0.124 AC: 1897 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5180

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10576

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10342 AN: 67982

Other (OTH) AF: 0.165 AC: 348 AN: 2106

Alfa AF: 0.158 Hom.: 1990

Bravo AF: 0.145

Asia WGS AF: 0.242 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.56
PhyloP100		-0.0020
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: rs7595299; hg19: chr2-43480317;