Genetic Variant NM_018951.4:c.1203G>A (chr7-27171929-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_018951.4(HOXA10):c.1203G>A(p.Arg401Arg) 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 (no stars).

Frequency

Genomes: 𝑓 0.025 ( 73 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1029 hom. )

Consequence

HOXA10
NM_018951.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0840

Publications

12 publications found

Variant links:

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]

HOXA10 links:

HOXA10-HOXA9 (HGNC:51908):

HOXA10-HOXA9 links:

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]

HOXA9 links:

ENSG00000293630 (HGNC:):

ENSG00000293630 links:

HOXA10-AS (HGNC:40281): (HOXA10 antisense RNA)

HOXA10-AS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 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 VariationId is 3056353.Status of the report is no_assertion_criteria_provided, 0 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3823 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018951.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA10	NM_018951.4	MANE Select	c.1203G>A	p.Arg401Arg	synonymous	Exon 2 of 2	NP_061824.3
HOXA10-HOXA9	NM_001433944.1		c.11-6962G>A		intron	N/A	NP_001420873.1	D6RAR5
HOXA10	NR_037939.2		n.461G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA10	ENST00000283921.5	TSL:1 MANE Select	c.1203G>A	p.Arg401Arg	synonymous	Exon 2 of 2	ENSP00000283921.4	P31260-1
HOXA10	ENST00000396344.4	TSL:1	c.255G>A	p.Arg85Arg	synonymous	Exon 2 of 2	ENSP00000379633.4	P31260-2
HOXA10-HOXA9	ENST00000470747.5	TSL:3	c.11-6962G>A		intron	N/A	ENSP00000421799.3

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3822

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0210

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.0350

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0258

AC:

6490

AN:

251488

AF XY:

0.0266

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.0411

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0349

AC:

51038

AN:

1461812

Hom.:

1029

Cov.:

AF XY:

0.0344

AC XY:

25008

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00535

AC:

179

AN:

33480

American (AMR)

AF:

0.0166

AC:

741

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

393

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00769

AC:

663

AN:

86256

European-Finnish (FIN)

AF:

0.0298

AC:

1593

AN:

53418

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0410

AC:

45618

AN:

1111938

Other (OTH)

AF:

0.0292

AC:

1766

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2688

5376

8065

10753

13441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1650

3300

4950

6600

8250

<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:

0.0251

AC:

3823

AN:

152248

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

1848

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00703

AC:

292

AN:

41556

American (AMR)

AF:

0.0210

AC:

321

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00643

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0350

AC:

371

AN:

10596

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0394

AC:

2677

AN:

68018

Other (OTH)

AF:

0.0279

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

195

390

585

780

975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0322

Hom.:

Bravo

AF:

0.0242

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0385

EpiControl

AF:

0.0437

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

HOXA10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.084

Mutation Taster

=91/9

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