dbSNP rs3757640: HOXA3:c.-493-2440G>A (chr7-27142626-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_153631.3(HOXA3):c.-493-2440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 189,504 control chromosomes in the GnomAD database, including 38,591 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 0.61 ( 29690 hom., cov: 33)

Exomes 𝑓: 0.67 ( 8901 hom. )

Consequence

HOXA3
NM_153631.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.225

Publications

13 publications found

Variant links:

Genes affected

HOXA3 (HGNC:5104): (homeobox A3) 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. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA3 links:

HOXA5 (HGNC:5106): (homeobox A5) 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. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis. [provided by RefSeq, Jul 2008]

HOXA5 links:

ENSG00000273433 (HGNC:):

ENSG00000273433 links:

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

HOXA-AS3 links:

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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=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA3	NM_153631.3 link	c.-493-2440G>A		intron_variant	Intron 1 of 5	ENST00000612286.5	NP_705895.1	O43365A4D182A0A024RA33B3KPN8
HOXA5	NM_019102.4 link	c.562+420G>A		intron_variant	Intron 1 of 1	ENST00000222726.4	NP_061975.2	P20719

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA3	ENST00000612286.5 link	c.-493-2440G>A		intron_variant	Intron 1 of 5	2	NM_153631.3	ENSP00000484411.1		O43365
HOXA5	ENST00000222726.4 link	c.562+420G>A		intron_variant	Intron 1 of 1	1	NM_019102.4	ENSP00000222726.3		P20719

Frequencies

GnomAD3 genomes

AF:

0.607

AC:

92206

AN:

151958

Hom.:

29683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.739

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.719

Gnomad OTH

AF:

0.652

GnomAD4 exome

AF:

0.675

AC:

25256

AN:

37428

Hom.:

8901

AF XY:

0.682

AC XY:

12687

AN XY:

18604

show subpopulations

African (AFR)

AF:

0.345

AC:

465

AN:

1346

American (AMR)

AF:

0.582

AC:

1152

AN:

1978

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

960

AN:

1312

East Asian (EAS)

AF:

0.620

AC:

1219

AN:

1966

South Asian (SAS)

AF:

0.728

AC:

719

AN:

988

European-Finnish (FIN)

AF:

0.585

AC:

974

AN:

1664

Middle Eastern (MID)

AF:

0.739

AC:

136

AN:

184

European-Non Finnish (NFE)

AF:

0.707

AC:

18080

AN:

25568

Other (OTH)

AF:

0.640

AC:

1551

AN:

2422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

367

734

1100

1467

1834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.607

AC:

92241

AN:

152076

Hom.:

29690

Cov.:

AF XY:

0.604

AC XY:

44897

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.382

AC:

15852

AN:

41454

American (AMR)

AF:

0.627

AC:

9580

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.761

AC:

2642

AN:

3470

East Asian (EAS)

AF:

0.612

AC:

3161

AN:

5164

South Asian (SAS)

AF:

0.740

AC:

3567

AN:

4822

European-Finnish (FIN)

AF:

0.599

AC:

6343

AN:

10586

Middle Eastern (MID)

AF:

0.741

AC:

218

AN:

294

European-Non Finnish (NFE)

AF:

0.719

AC:

48917

AN:

67990

Other (OTH)

AF:

0.652

AC:

1375

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1728

3456

5185

6913

8641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.700

Hom.:

50131

Bravo

AF:

0.595

Asia WGS

AF:

0.645

AC:

2243

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.23

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