Genetic Variant HOXA7:c.*432C>A (chr7-27154477-G-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.*432C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 168,650 control chromosomes in the GnomAD database, including 562 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 0.050 ( 558 hom., cov: 33)

Exomes 𝑓: 0.0085 ( 4 hom. )

Consequence

HOXA7
NM_006896.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0630

Publications

1 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:

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

HOXA-AS3 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 (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HOXA7	NM_006896.4 link	c.*432C>A	3_prime_UTR_variant	Exon 2 of 2	ENST00000242159.5	NP_008827.2	P31268
HOXA-AS3	NR_038831.1 link	n.2541G>T	non_coding_transcript_exon_variant	Exon 3 of 3
HOXA-AS3	NR_038832.1 link	n.2467G>T	non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA7	ENST00000242159.5 link	c.*432C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_006896.4	ENSP00000242159.3		P31268
HOXA-AS3	ENST00000518947.6 link	n.2541G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7563

AN:

152116

Hom.:

558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0191

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.00268

Gnomad OTH

AF:

0.0430

GnomAD4 exome

AF:

0.00853

AC:

140

AN:

16418

Hom.:

Cov.:

AF XY:

0.00950

AC XY:

AN XY:

8528

show subpopulations

African (AFR)

AF:

0.147

AC:

AN:

306

American (AMR)

AF:

0.0169

AC:

AN:

2430

Ashkenazi Jewish (ASJ)

AF:

0.00926

AC:

AN:

324

East Asian (EAS)

AF:

0.00

AC:

AN:

804

South Asian (SAS)

AF:

0.0141

AC:

AN:

1416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

738

Middle Eastern (MID)

AF:

0.0263

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00178

AC:

AN:

9576

Other (OTH)

AF:

0.0165

AC:

AN:

786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0497

AC:

7569

AN:

152232

Hom.:

558

Cov.:

AF XY:

0.0496

AC XY:

3695

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.164

AC:

6798

AN:

41496

American (AMR)

AF:

0.0242

AC:

370

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.0185

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00268

AC:

182

AN:

68028

Other (OTH)

AF:

0.0426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

331

662

993

1324

1655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0160

Hom.:

Bravo

AF:

0.0573

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

(source)

DANN

Benign

0.54

PhyloP100

0.063

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

Publications

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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