dbSNP rs13390932: HOXD1:c.653-125T>C (chr2-176189683-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024501.3(HOXD1):c.653-125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,600,720 control chromosomes in the GnomAD database, including 66,377 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 0.31 ( 7851 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58526 hom. )

Consequence

HOXD1
NM_024501.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.390

Publications

15 publications found

Variant links:

Genes affected

HOXD1 (HGNC:5132): (homeobox D1) This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. This nuclear protein functions as a sequence-specific transcription factor that is involved in differentiation and limb development. Mutations in this gene have been associated with severe developmental defects on the anterior-posterior (a-p) limb axis. [provided by RefSeq, Jul 2008]

HOXD1 links:

ENSG00000279160 (HGNC:):

ENSG00000279160 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024501.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD1	NM_024501.3	MANE Select	c.653-125T>C		intron	N/A	NP_078777.1	Q9GZZ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOXD1	ENST00000331462.6	TSL:1 MANE Select	c.653-125T>C	intron	N/A	ENSP00000328598.4	Q9GZZ0
HOXD1	ENST00000876788.1		c.880+2T>C	splice_donor intron	N/A	ENSP00000546847.1
ENSG00000279160	ENST00000623777.1	TSL:6	n.*236A>G	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46648

AN:

151892

Hom.:

7827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.0211

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.311

GnomAD2 exomes

AF:

0.245

AC:

54724

AN:

222958

AF XY:

0.246

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.0231

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.276

AC:

399171

AN:

1448710

Hom.:

58526

Cov.:

AF XY:

0.272

AC XY:

196108

AN XY:

719906

show subpopulations

African (AFR)

AF:

0.434

AC:

14389

AN:

33176

American (AMR)

AF:

0.168

AC:

7065

AN:

41940

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

8870

AN:

25884

East Asian (EAS)

AF:

0.0149

AC:

587

AN:

39298

South Asian (SAS)

AF:

0.166

AC:

14048

AN:

84698

European-Finnish (FIN)

AF:

0.262

AC:

13590

AN:

51958

Middle Eastern (MID)

AF:

0.270

AC:

1555

AN:

5764

European-Non Finnish (NFE)

AF:

0.292

AC:

322414

AN:

1105974

Other (OTH)

AF:

0.277

AC:

16653

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

14751

29503

44254

59006

73757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10586

21172

31758

42344

52930

<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:

0.307

AC:

46721

AN:

152010

Hom.:

7851

Cov.:

AF XY:

0.301

AC XY:

22384

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.428

AC:

17731

AN:

41450

American (AMR)

AF:

0.233

AC:

3565

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1197

AN:

3470

East Asian (EAS)

AF:

0.0212

AC:

109

AN:

5144

South Asian (SAS)

AF:

0.153

AC:

740

AN:

4824

European-Finnish (FIN)

AF:

0.256

AC:

2709

AN:

10590

Middle Eastern (MID)

AF:

0.267

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.290

AC:

19685

AN:

67948

Other (OTH)

AF:

0.309

AC:

653

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1593

3187

4780

6374

7967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.303

Hom.:

18671

Bravo

AF:

0.314

Asia WGS

AF:

0.116

AC:

406

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

9.5

(source)

DANN

Benign

0.66

PhyloP100

-0.39

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over