Genetic Variant HOXA4:c.*125G>C (chr7-27129100-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002141.5(HOXA4):c.*125G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXA4
NM_002141.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

6 publications found

Variant links:

Genes affected

HOXA4 (HGNC:5105): (homeobox A4) 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. [provided by RefSeq, Jul 2008]

HOXA4 links:

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:

ENSG00000273433 (HGNC:):

ENSG00000273433 links:

HOXA-AS2 (HGNC:43745): (HOXA cluster antisense RNA 2) This gene produces a long non-coding RNA that promotes cell proliferation. This transcript may interact with enhancer of zeste homolog 2 Polycomb repressive complex to repress gene expression. [provided by RefSeq, Dec 2017]

HOXA-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002141.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOXA4	NM_002141.5	MANE Select	c.*125G>C	3_prime_UTR	Exon 2 of 2	NP_002132.3
HOXA3	NM_153631.3	MANE Select	c.-389-2030G>C	intron	N/A	NP_705895.1	O43365
HOXA3	NM_001384335.1		c.-505-2030G>C	intron	N/A	NP_001371264.1	O43365

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOXA4	ENST00000360046.10	TSL:1 MANE Select	c.*125G>C	3_prime_UTR	Exon 2 of 2	ENSP00000353151.5	Q00056
HOXA4	ENST00000610970.1	TSL:1	c.*125G>C	3_prime_UTR	Exon 2 of 2	ENSP00000479166.1	Q00056
HOXA4	ENST00000511914.1	TSL:1	c.*125G>C	3_prime_UTR	Exon 2 of 2	ENSP00000448015.1	H0YHX3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

576972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

311528

African (AFR)

AF:

0.00

AC:

AN:

15622

American (AMR)

AF:

0.00

AC:

AN:

35216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17794

East Asian (EAS)

AF:

0.00

AC:

AN:

35606

South Asian (SAS)

AF:

0.00

AC:

AN:

60816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

334290

Other (OTH)

AF:

0.00

AC:

AN:

30666

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68054

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

36264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over