rs847151
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_021193.4(HOXD12):c.375G>A(p.Leu125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,611,982 control chromosomes in the GnomAD database, including 91,941 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 0.36 ( 10378 hom., cov: 34)
Exomes 𝑓: 0.33 ( 81563 hom. )
Consequence
HOXD12
NM_021193.4 synonymous
NM_021193.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.33
Genes affected
HOXD12 (HGNC:5135): (homeobox D12) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The exact role of this gene has not been determined. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP7
?
Synonymous conserved (PhyloP=3.33 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOXD12 | NM_021193.4 | c.375G>A | p.Leu125= | synonymous_variant | 1/2 | ENST00000406506.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXD12 | ENST00000406506.4 | c.375G>A | p.Leu125= | synonymous_variant | 1/2 | 3 | NM_021193.4 | P1 | |
HOXD12 | ENST00000404162.2 | c.375G>A | p.Leu125= | synonymous_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.356 AC: 54197AN: 152108Hom.: 10360 Cov.: 34
GnomAD3 genomes
?
AF:
AC:
54197
AN:
152108
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.314 AC: 75844AN: 241292Hom.: 13232 AF XY: 0.305 AC XY: 40356AN XY: 132210
GnomAD3 exomes
AF:
AC:
75844
AN:
241292
Hom.:
AF XY:
AC XY:
40356
AN XY:
132210
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.327 AC: 477250AN: 1459756Hom.: 81563 Cov.: 42 AF XY: 0.323 AC XY: 234594AN XY: 726148
GnomAD4 exome
AF:
AC:
477250
AN:
1459756
Hom.:
Cov.:
42
AF XY:
AC XY:
234594
AN XY:
726148
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.356 AC: 54253AN: 152226Hom.: 10378 Cov.: 34 AF XY: 0.350 AC XY: 26020AN XY: 74440
GnomAD4 genome
?
AF:
AC:
54253
AN:
152226
Hom.:
Cov.:
34
AF XY:
AC XY:
26020
AN XY:
74440
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
675
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at