rs34957925
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_018951.4(HOXA10):c.1203G>A(p.Arg401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,614,060 control chromosomes in the GnomAD database, including 1,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.025 ( 73 hom., cov: 33)
Exomes 𝑓: 0.035 ( 1029 hom. )
Consequence
HOXA10
NM_018951.4 synonymous
NM_018951.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0840
Genes affected
HOXA10 (HGNC:5100): (homeobox A10) 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 that may regulate gene expression, morphogenesis, and differentiation. More specifically, it may function in fertility, embryo viability, and regulation of hematopoietic lineage commitment. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the downstream homeobox A9 (HOXA9) gene. [provided by RefSeq, Mar 2011]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 7-27171929-C-T is Benign according to our data. Variant chr7-27171929-C-T is described in ClinVar as [Benign]. Clinvar id is 3056353.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.084 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3823/152248) while in subpopulation NFE AF= 0.0394 (2677/68018). AF 95% confidence interval is 0.0381. There are 73 homozygotes in gnomad4. There are 1848 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 3823 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOXA10 | NM_018951.4 | c.1203G>A | p.Arg401= | synonymous_variant | 2/2 | ENST00000283921.5 | |
HOXA10-HOXA9 | NR_037940.1 | n.617-6962G>A | intron_variant, non_coding_transcript_variant | ||||
HOXA10 | NR_037939.2 | n.461G>A | non_coding_transcript_exon_variant | 2/2 | |||
HOXA10-AS | NR_046609.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXA10 | ENST00000283921.5 | c.1203G>A | p.Arg401= | synonymous_variant | 2/2 | 1 | NM_018951.4 | P2 | |
HOXA10-AS | ENST00000519935.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0251 AC: 3822AN: 152130Hom.: 72 Cov.: 33
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GnomAD3 exomes AF: 0.0258 AC: 6490AN: 251488Hom.: 131 AF XY: 0.0266 AC XY: 3610AN XY: 135920
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GnomAD4 exome AF: 0.0349 AC: 51038AN: 1461812Hom.: 1029 Cov.: 32 AF XY: 0.0344 AC XY: 25008AN XY: 727224
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GnomAD4 genome ? AF: 0.0251 AC: 3823AN: 152248Hom.: 73 Cov.: 33 AF XY: 0.0248 AC XY: 1848AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HOXA10-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 10, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at