Genetic Variant HOXA7:p.Ala18Thr (chr7-27156494-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006896.4(HOXA7):c.52G>A(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,596,288 control chromosomes in the GnomAD database, including 529,356 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 37874 hom., cov: 35)

Exomes 𝑓: 0.82 ( 491482 hom. )

Consequence

HOXA7
NM_006896.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.44

Publications

35 publications found

Variant links:

Genes affected

HOXA7 (HGNC:5108): (homeobox A7) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. For example, the encoded protein represses the transcription of differentiation-specific genes during keratinocyte proliferation, but this repression is then overcome by differentiation signals. This gene is highly similar to the antennapedia (Antp) gene of Drosophila. [provided by RefSeq, Jul 2008]

HOXA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=2.8064014E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA7	NM_006896.4 link	c.52G>A	p.Ala18Thr	missense_variant	Exon 1 of 2	ENST00000242159.5	NP_008827.2	P31268

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA7	ENST00000242159.5 link	c.52G>A	p.Ala18Thr	missense_variant	Exon 1 of 2	1	NM_006896.4	ENSP00000242159.3		P31268
HOXA7	ENST00000519842.1 link	c.52G>A	p.Ala18Thr	missense_variant	Exon 3 of 3	3		ENSP00000428563.1		E5RHM9

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

98284

AN:

152106

Hom.:

37875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.916

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.819

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.841

Gnomad OTH

AF:

0.692

GnomAD2 exomes

AF:

0.773

AC:

188237

AN:

243600

AF XY:

0.788

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.684

Gnomad ASJ exome

AF:

0.869

Gnomad EAS exome

AF:

0.865

Gnomad FIN exome

AF:

0.806

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.818

AC:

1181243

AN:

1444064

Hom.:

491482

Cov.:

AF XY:

0.820

AC XY:

587226

AN XY:

715954

show subpopulations

African (AFR)

AF:

0.167

AC:

5460

AN:

32642

American (AMR)

AF:

0.681

AC:

29456

AN:

43240

Ashkenazi Jewish (ASJ)

AF:

0.866

AC:

22093

AN:

25520

East Asian (EAS)

AF:

0.854

AC:

33610

AN:

39338

South Asian (SAS)

AF:

0.822

AC:

69702

AN:

84832

European-Finnish (FIN)

AF:

0.814

AC:

43073

AN:

52914

Middle Eastern (MID)

AF:

0.816

AC:

4652

AN:

5700

European-Non Finnish (NFE)

AF:

0.841

AC:

925847

AN:

1100274

Other (OTH)

AF:

0.794

AC:

47350

AN:

59604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

10205

20410

30614

40819

51024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20874

41748

62622

83496

104370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.646

AC:

98299

AN:

152224

Hom.:

37874

Cov.:

AF XY:

0.648

AC XY:

48234

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.195

AC:

8098

AN:

41548

American (AMR)

AF:

0.693

AC:

10605

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

2994

AN:

3470

East Asian (EAS)

AF:

0.849

AC:

4398

AN:

5180

South Asian (SAS)

AF:

0.820

AC:

3958

AN:

4828

European-Finnish (FIN)

AF:

0.805

AC:

8535

AN:

10596

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.841

AC:

57184

AN:

67984

Other (OTH)

AF:

0.693

AC:

1465

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1180

2361

3541

4722

5902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.782

Hom.:

189617

Bravo

AF:

0.613

TwinsUK

AF:

0.841

AC:

3117

ALSPAC

AF:

0.845

AC:

3258

ESP6500AA

AF:

0.210

AC:

924

ESP6500EA

AF:

0.835

AC:

7180

ExAC

AF:

0.767

AC:

93000

Asia WGS

AF:

0.792

AC:

2755

AN:

3478

EpiCase

AF:

0.843

EpiControl

AF:

0.836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.069

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0000028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.39

N;.

PhyloP100

2.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.021

Sift

Benign

0.33

T;.

Sift4G

Benign

0.44

T;.

Polyphen

0.080

B;.

Vest4

0.068

MPC

0.38

ClinPred

0.014

GERP RS

4.3

PromoterAI

0.070

Neutral

(source)

Varity_R

0.075

gMVP

0.48

Mutation Taster

=88/12

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over