NM_022065.5:c.4439-11950G>A

Variant names:

• chr2-43305163-C-T
• rs11891936
• NM_022065.5:c.4439-11950G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022065.5(THADA):​c.4439-11950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,974 control chromosomes in the GnomAD database, including 2,684 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 0.18 (2684 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 7 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=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 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.4439-11950G>A		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.4439-11950G>A		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.4439-11950G>A		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.4439-11950G>A		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.4439-11950G>A		intron	N/A	ENSP00000385995.4
	THADA	ENST00000407351.5	TSL:2	c.2156-11950G>A		intron	N/A	ENSP00000386112.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27788 AN: 151856 Hom.: 2680 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.183 AC: 27803 AN: 151974 Hom.: 2684 Cov.: 32 AF XY: 0.184 AC XY: 13676 AN XY: 74274

African (AFR) AF: 0.160 AC: 6638 AN: 41446

American (AMR) AF: 0.146 AC: 2229 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1162 AN: 5174

South Asian (SAS) AF: 0.268 AC: 1290 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2045 AN: 10524

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12905 AN: 67948

Other (OTH) AF: 0.193 AC: 408 AN: 2112

Alfa AF: 0.192 Hom.: 1301

Bravo AF: 0.179

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		0.049
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: rs11891936; hg19: chr2-43532302;