dbSNP rs847151: HOXD12:p.Leu125Leu (chr2-176100176-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

19 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HOXD12	NM_021193.4 link	c.375G>A	p.Leu125Leu	synonymous_variant	Exon 1 of 2	ENST00000406506.4	NP_067016.3	P35452-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD12	ENST00000406506.4 link	c.375G>A	p.Leu125Leu	synonymous_variant	Exon 1 of 2	3	NM_021193.4	ENSP00000385586.2		P35452-1
HOXD12	ENST00000404162.2 link	c.375G>A	p.Leu125Leu	synonymous_variant	Exon 1 of 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

GnomAD2 exomes

AF:

0.314

AC:

75844

AN:

241292

AF XY:

0.305

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 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

African (AFR)

AF:

0.482

AC:

16117

AN:

33464

American (AMR)

AF:

0.437

AC:

19490

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

7174

AN:

26096

East Asian (EAS)

AF:

0.0473

AC:

1876

AN:

39688

South Asian (SAS)

AF:

0.235

AC:

20294

AN:

86206

European-Finnish (FIN)

AF:

0.290

AC:

15073

AN:

51974

Middle Eastern (MID)

AF:

0.298

AC:

1719

AN:

5760

European-Non Finnish (NFE)

AF:

0.338

AC:

376086

AN:

1111600

Other (OTH)

AF:

0.322

AC:

19421

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

20357

40715

61072

81430

101787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12206

24412

36618

48824

61030

<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:

0.356

AC:

54253

AN:

152226

Hom.:

10378

Cov.:

AF XY:

0.350

AC XY:

26020

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.473

AC:

19645

AN:

41540

American (AMR)

AF:

0.375

AC:

5734

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

997

AN:

3470

East Asian (EAS)

AF:

0.0637

AC:

329

AN:

5168

South Asian (SAS)

AF:

0.225

AC:

1088

AN:

4828

European-Finnish (FIN)

AF:

0.296

AC:

3136

AN:

10604

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22477

AN:

67996

Other (OTH)

AF:

0.338

AC:

713

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1814

3628

5442

7256

9070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.338

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

(source)

DANN

Benign

0.90

PhyloP100

3.3

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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