Variant rs847151 details in Genebe, Genetics Data Aggregator

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.Leu125Leu) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.33

Variant links:

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]

HOXD12 links:

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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	Protein	UniProt
HOXD12	NM_021193.4 link	c.375G>A	p.Leu125Leu	synonymous_variant	1/2	ENST00000406506.4	NP_067016.3	P35452-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD12	ENST00000406506.4 link	c.375G>A	p.Leu125Leu	synonymous_variant	1/2	3	NM_021193.4	ENSP00000385586.2		P35452-1
HOXD12	ENST00000404162.2 link	c.375G>A	p.Leu125Leu	synonymous_variant	1/2	1		ENSP00000385132.2		B5MCD3

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54197

AN:

152108

Hom.:

10360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0641

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.337

GnomAD3 exomes

AF:

0.314

AC:

75844

AN:

241292

Hom.:

13232

AF XY:

0.305

AC XY:

40356

AN XY:

132210

show subpopulations

Gnomad AFR exome

AF:

0.485

Gnomad AMR exome

AF:

0.443

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.0636

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.321

GnomAD4 exome

AF:

0.327

AC:

477250

AN:

1459756

Hom.:

81563

Cov.:

AF XY:

0.323

AC XY:

234594

AN XY:

726148

show subpopulations

Gnomad4 AFR exome

AF:

0.482

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.0473

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.356

AC:

54253

AN:

152226

Hom.:

10378

Cov.:

AF XY:

0.350

AC XY:

26020

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.0637

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.338

Hom.:

3830

Bravo

AF:

0.369

Asia WGS

AF:

0.193

AC:

675

AN:

3478

EpiCase

AF:

0.326

EpiControl

AF:

0.322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over