rs13414140

Variant names:

• chr2-43444037-C-T
• rs13414140
• NM_022065.5:c.3837-13735G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):​c.3837-13735G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,066 control chromosomes in the GnomAD database, including 3,010 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 (3010 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.3837-13735G>A		intron_variant	Intron 26 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.3837-13735G>A		intron_variant	Intron 26 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25134 AN: 151948 Hom.: 2993 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0570

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.166 AC: 25194 AN: 152066 Hom.: 3010 Cov.: 32 AF XY: 0.159 AC XY: 11841 AN XY: 74352

African (AFR) AF: 0.333 AC: 13814 AN: 41464

American (AMR) AF: 0.0990 AC: 1510 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3468

East Asian (EAS) AF: 0.00657 AC: 34 AN: 5174

South Asian (SAS) AF: 0.146 AC: 707 AN: 4828

European-Finnish (FIN) AF: 0.0570 AC: 603 AN: 10580

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7641 AN: 67982

Other (OTH) AF: 0.139 AC: 293 AN: 2110

Alfa AF: 0.124 Hom.: 1176

Bravo AF: 0.173

Asia WGS AF: 0.0760 AC: 266 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	1.7
DANN	Benign	0.59
PhyloP100		-0.36
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: rs13414140; hg19: chr2-43671176;