Genetic Variant HOXA9:n.1323T>C (chr7-27162670-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000497089.1(HOXA9):n.1323T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 209,434 control chromosomes in the GnomAD database, including 56,481 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 0.72 ( 39752 hom., cov: 33)

Exomes 𝑓: 0.76 ( 16729 hom. )

Consequence

HOXA9
ENST00000497089.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.86

Publications

35 publications found

Variant links:

Genes affected

HOXA9 (HGNC:5109): (homeobox A9) 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. This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis. Read-through transcription exists between this gene and the upstream homeobox A10 (HOXA10) gene.[provided by RefSeq, Mar 2011]

HOXA9 links:

HOXA10-HOXA9 (HGNC:51908):

HOXA10-HOXA9 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA9	NM_152739.4 link	c.*933T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000343483.7	NP_689952.1	P31269
HOXA10-HOXA9	NM_001433944.1 link	c.*933T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001420873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA9	ENST00000497089.1 link	n.1323T>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
HOXA9	ENST00000343483.7 link	c.*933T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_152739.4	ENSP00000343619.6		P31269

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109242

AN:

152012

Hom.:

39732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.857

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.707

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.751

GnomAD4 exome

AF:

0.761

AC:

43616

AN:

57304

Hom.:

16729

Cov.:

AF XY:

0.764

AC XY:

20425

AN XY:

26744

show subpopulations

African (AFR)

AF:

0.642

AC:

1591

AN:

2478

American (AMR)

AF:

0.693

AC:

1132

AN:

1634

Ashkenazi Jewish (ASJ)

AF:

0.836

AC:

3055

AN:

3656

East Asian (EAS)

AF:

0.678

AC:

5832

AN:

8598

South Asian (SAS)

AF:

0.854

AC:

420

AN:

492

European-Finnish (FIN)

AF:

0.708

AC:

327

AN:

462

Middle Eastern (MID)

AF:

0.810

AC:

269

AN:

332

European-Non Finnish (NFE)

AF:

0.786

AC:

27381

AN:

34822

Other (OTH)

AF:

0.747

AC:

3609

AN:

4830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

526

1052

1577

2103

2629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.719

AC:

109312

AN:

152130

Hom.:

39752

Cov.:

AF XY:

0.717

AC XY:

53296

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.613

AC:

25397

AN:

41458

American (AMR)

AF:

0.702

AC:

10735

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.857

AC:

2974

AN:

3472

East Asian (EAS)

AF:

0.633

AC:

3275

AN:

5176

South Asian (SAS)

AF:

0.825

AC:

3973

AN:

4818

European-Finnish (FIN)

AF:

0.707

AC:

7484

AN:

10590

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.780

AC:

53041

AN:

68008

Other (OTH)

AF:

0.751

AC:

1585

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1575

3150

4724

6299

7874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.761

Hom.:

172056

Bravo

AF:

0.708

Asia WGS

AF:

0.733

AC:

2550

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0040

(source)

DANN

Benign

0.33

PhyloP100

-1.9

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