rs11897432

Variant names:

• chr2-43590366-G-A
• rs11897432
• NM_022065.5:c.302+458C>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.302+458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,940 control chromosomes in the GnomAD database, including 2,769 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 0.19 (2769 hom., cov: 31)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	NM_022065.5	MANE Select	c.302+458C>T		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.302+458C>T		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.302+458C>T		intron	N/A	NP_001332854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.302+458C>T		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.302+458C>T		intron	N/A	ENSP00000385995.4
	THADA	ENST00000404790.5	TSL:1	c.302+458C>T		intron	N/A	ENSP00000384266.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28191 AN: 151822 Hom.: 2764 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.186 AC: 28200 AN: 151940 Hom.: 2769 Cov.: 31 AF XY: 0.183 AC XY: 13586 AN XY: 74260

African (AFR) AF: 0.150 AC: 6205 AN: 41442

American (AMR) AF: 0.148 AC: 2261 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3466

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

South Asian (SAS) AF: 0.203 AC: 974 AN: 4798

European-Finnish (FIN) AF: 0.185 AC: 1954 AN: 10534

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15293 AN: 67942

Other (OTH) AF: 0.192 AC: 403 AN: 2104

Alfa AF: 0.210 Hom.: 10723

Bravo AF: 0.179

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.79
PhyloP100		-0.83
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: rs11897432; hg19: chr2-43817505;