Genetic Variant ENSG00000257184:c.11-696T>C (chr7-27165663-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 ENST00000470747.4(ENSG00000257184):c.11-696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 687,948 control chromosomes in the GnomAD database, including 188,751 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 0.73 ( 40339 hom., cov: 35)

Exomes 𝑓: 0.74 ( 148412 hom. )

Consequence

ENSG00000257184
ENST00000470747.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.20

Publications

23 publications found

Variant links:

Genes affected

ENSG00000257184 (HGNC:51908):

ENSG00000257184 links:

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:

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=-0.51).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA10-HOXA9	NM_001433944.1 link	c.11-696T>C		intron_variant	Intron 1 of 2		NP_001420873.1
HOXA9	NM_152739.4 link	c.-206T>C		upstream_gene_variant		ENST00000343483.7	NP_689952.1	P31269

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000257184	ENST00000470747.4 link	c.11-696T>C		intron_variant	Intron 1 of 2	3		ENSP00000421799.3		D6RAR5
HOXA9	ENST00000343483.7 link	c.-206T>C		upstream_gene_variant		1	NM_152739.4	ENSP00000343619.6		P31269

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110591

AN:

152126

Hom.:

40318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.727

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.735

GnomAD4 exome

AF:

0.743

AC:

397806

AN:

535704

Hom.:

148412

AF XY:

0.747

AC XY:

205025

AN XY:

274554

show subpopulations

African (AFR)

AF:

0.725

AC:

7859

AN:

10840

American (AMR)

AF:

0.664

AC:

8177

AN:

12316

Ashkenazi Jewish (ASJ)

AF:

0.773

AC:

10210

AN:

13214

East Asian (EAS)

AF:

0.677

AC:

17926

AN:

26486

South Asian (SAS)

AF:

0.810

AC:

34004

AN:

41978

European-Finnish (FIN)

AF:

0.696

AC:

20216

AN:

29062

Middle Eastern (MID)

AF:

0.750

AC:

1578

AN:

2104

European-Non Finnish (NFE)

AF:

0.746

AC:

277088

AN:

371436

Other (OTH)

AF:

0.734

AC:

20748

AN:

28268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5211

10423

15634

20846

26057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3650

7300

10950

14600

18250

<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:

0.727

AC:

110660

AN:

152244

Hom.:

40339

Cov.:

AF XY:

0.726

AC XY:

54018

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.727

AC:

30189

AN:

41546

American (AMR)

AF:

0.684

AC:

10470

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

2695

AN:

3472

East Asian (EAS)

AF:

0.637

AC:

3292

AN:

5168

South Asian (SAS)

AF:

0.805

AC:

3891

AN:

4832

European-Finnish (FIN)

AF:

0.685

AC:

7257

AN:

10598

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.743

AC:

50537

AN:

68010

Other (OTH)

AF:

0.735

AC:

1553

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1609

3218

4828

6437

8046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.739

Hom.:

50613

Bravo

AF:

0.722

Asia WGS

AF:

0.723

AC:

2517

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

2.2

PromoterAI

0.069

Neutral

(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