NM_022065.5:c.2948-1147A>T

Variant names:

• chr2-43550515-T-A
• rs11903287
• NM_022065.5:c.2948-1147A>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.2948-1147A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,908 control chromosomes in the GnomAD database, including 8,707 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 0.33 (8707 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 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.2948-1147A>T		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.2948-1147A>T		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.2948-1147A>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.2948-1147A>T		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.2948-1147A>T		intron	N/A	ENSP00000385995.4
	THADA	ENST00000408045.7	TSL:1	n.*2043-1147A>T		intron	N/A	ENSP00000384172.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50310 AN: 151790 Hom.: 8700 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.331 AC: 50343 AN: 151908 Hom.: 8707 Cov.: 32 AF XY: 0.328 AC XY: 24365 AN XY: 74220

African (AFR) AF: 0.415 AC: 17171 AN: 41386

American (AMR) AF: 0.236 AC: 3595 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1354 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1312 AN: 5170

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4812

European-Finnish (FIN) AF: 0.287 AC: 3028 AN: 10546

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20859 AN: 67956

Other (OTH) AF: 0.312 AC: 656 AN: 2104

Alfa AF: 0.303 Hom.: 898

Bravo AF: 0.329

Asia WGS AF: 0.345 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.60
PhyloP100		0.45
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: rs11903287; hg19: chr2-43777654;