Variant 7-27156494-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HOXA7	NM_006896.4 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	1/2	ENST00000242159.5	NP_008827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA7	ENST00000242159.5 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	1/2	1	NM_006896.4	ENSP00000242159	P1
HOXA7	ENST00000519842.1 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	3/3	3		ENSP00000428563

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

GnomAD3 exomes

AF:

0.773

AC:

188237

AN:

243600

Hom.:

76167

AF XY:

0.788

AC XY:

104148

AN XY:

132110

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 SAS exome

AF:

0.824

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

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.681

Gnomad4 ASJ exome

AF:

0.866

Gnomad4 EAS exome

AF:

0.854

Gnomad4 SAS exome

AF:

0.822

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.841

Gnomad4 OTH exome

AF:

0.794

GnomAD4 genome

AF:

0.646

AC:

98299

AN:

152224

Hom.:

37874

Cov.:

AF XY:

0.648

AC XY:

48234

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.863

Gnomad4 EAS

AF:

0.849

Gnomad4 SAS

AF:

0.820

Gnomad4 FIN

AF:

0.805

Gnomad4 NFE

AF:

0.841

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.815

Hom.:

101705

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

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;.

MutationTaster

Benign

0.016

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

Varity_R

0.075

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over