7-27095697-ATGGTGGTGGTGG-ATGGTGGTGGTGGTGG

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_005522.5(HOXA1):c.213_215dupCCA(p.His72dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 949,602 control chromosomes in the GnomAD database, including 35 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. H72H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0082 ( 17 hom., cov: 30)

Exomes 𝑓: 0.0040 ( 18 hom. )

Consequence

HOXA1
NM_005522.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.59

Publications

3 publications found

Variant links:

Genes affected

HOXA1 (HGNC:5099): (homeobox A1) 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. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region. [provided by RefSeq, Jul 2008]

HOXA1 links:

HOTAIRM1 (HGNC:37117): (HOXA transcript antisense RNA, myeloid-specific 1) This non-coding locus is located in the HOX gene cluster. Transcription of this locus is induced by retinoic acid, and transcripts likely function in regulation of myelopoiesis through transcriptional activation of several genes in the HOXA cluster, in addition to several beta-2 integrins. [provided by RefSeq, Jan 2013]

HOTAIRM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005522.5

BP6

Variant 7-27095697-A-ATGG is Benign according to our data. Variant chr7-27095697-A-ATGG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 587851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00816 (1156/141604) while in subpopulation AFR AF = 0.023 (925/40226). AF 95% confidence interval is 0.0218. There are 17 homozygotes in GnomAd4. There are 544 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005522.5. 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
	HOXA1	NM_005522.5	MANE Select	c.213_215dupCCA	p.His72dup	disruptive_inframe_insertion	Exon 1 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.213_215dupCCA	p.His72dup	disruptive_inframe_insertion	Exon 1 of 3	NP_705873.3	P49639-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA1	ENST00000643460.2	MANE Select	c.213_215dupCCA	p.His72dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000494260.2	P49639-1
HOXA1	ENST00000355633.5	TSL:1	c.213_215dupCCA	p.His72dup	disruptive_inframe_insertion	Exon 1 of 3	ENSP00000347851.5	E7ERT8
HOTAIRM1	ENST00000495032.1	TSL:5	n.26+47_26+49dupTGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00819

AC:

1158

AN:

141478

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00391

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0157

Gnomad SAS

AF:

0.00446

Gnomad FIN

AF:

0.000838

Gnomad MID

AF:

0.00690

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00571

GnomAD2 exomes

AF:

0.00386

AC:

897

AN:

232380

AF XY:

0.00340

show subpopulations

Gnomad AFR exome

AF:

0.0230

Gnomad AMR exome

AF:

0.00277

Gnomad ASJ exome

AF:

0.000110

Gnomad EAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.000304

Gnomad NFE exome

AF:

0.000901

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00404

AC:

3263

AN:

807998

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

1593

AN XY:

388544

show subpopulations

African (AFR)

AF:

0.0290

AC:

727

AN:

25096

American (AMR)

AF:

0.00755

AC:

124

AN:

16414

Ashkenazi Jewish (ASJ)

AF:

0.000166

AC:

AN:

12046

East Asian (EAS)

AF:

0.0398

AC:

681

AN:

17094

South Asian (SAS)

AF:

0.0115

AC:

292

AN:

25502

European-Finnish (FIN)

AF:

0.00127

AC:

AN:

20436

Middle Eastern (MID)

AF:

0.00529

AC:

AN:

3402

European-Non Finnish (NFE)

AF:

0.00180

AC:

1182

AN:

655772

Other (OTH)

AF:

0.00655

AC:

211

AN:

32236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

193

386

579

772

965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00816

AC:

1156

AN:

141604

Hom.:

Cov.:

AF XY:

0.00786

AC XY:

544

AN XY:

69192

show subpopulations

African (AFR)

AF:

0.0230

AC:

925

AN:

40226

American (AMR)

AF:

0.00391

AC:

AN:

14084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3162

East Asian (EAS)

AF:

0.0159

AC:

AN:

4656

South Asian (SAS)

AF:

0.00446

AC:

AN:

4264

European-Finnish (FIN)

AF:

0.000838

AC:

AN:

9550

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.000991

AC:

AN:

62556

Other (OTH)

AF:

0.00565

AC:

AN:

1948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=72/28

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over