Genetic Variant NM_022065.5:c.4344-6270A>G (chr2-43326810-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022065.5(THADA):c.4344-6270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,146 control chromosomes in the GnomAD database, including 48,417 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 0.79 ( 48417 hom., cov: 31)

Consequence

THADA
NM_022065.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.129

Publications

118 publications found

Variant links:

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]

THADA links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_022065.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THADA	NM_022065.5	MANE Select	c.4344-6270A>G	intron	N/A	NP_071348.3
THADA	NM_001083953.2		c.4344-6270A>G	intron	N/A	NP_001077422.1	Q6YHU6-1
THADA	NM_001345925.2		c.4344-6270A>G	intron	N/A	NP_001332854.1	Q6YHU6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THADA	ENST00000405975.7	TSL:1 MANE Select	c.4344-6270A>G	intron	N/A	ENSP00000386088.2	Q6YHU6-1
THADA	ENST00000405006.8	TSL:1	c.4344-6270A>G	intron	N/A	ENSP00000385995.4	Q6YHU6-1
THADA	ENST00000855634.1		c.4344-6270A>G	intron	N/A	ENSP00000525693.1

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119821

AN:

152028

Hom.:

48372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.892

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.811

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.787

Gnomad OTH

AF:

0.766

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

GnomAD4 genome

AF:

0.788

AC:

119921

AN:

152146

Hom.:

48417

Cov.:

AF XY:

0.784

AC XY:

58334

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.892

AC:

37016

AN:

41508

American (AMR)

AF:

0.654

AC:

9993

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.834

AC:

2897

AN:

3472

East Asian (EAS)

AF:

0.283

AC:

1464

AN:

5166

South Asian (SAS)

AF:

0.806

AC:

3884

AN:

4820

European-Finnish (FIN)

AF:

0.811

AC:

8593

AN:

10600

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.787

AC:

53477

AN:

67982

Other (OTH)

AF:

0.763

AC:

1610

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1205

2410

3615

4820

6025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.776

Hom.:

157285

Bravo

AF:

0.774

Asia WGS

AF:

0.567

AC:

1970

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

3.0

(source)

DANN

Benign

0.79

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over