7-27095697-ATGGTGGTGG-A

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.207_215delCCACCACCA(p.His70_His72del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00329 in 949,682 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. H69H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 30)

Exomes 𝑓: 0.0035 ( 22 hom. )

Consequence

HOXA1
NM_005522.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.23

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:

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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-ATGGTGGTGG-A is Benign according to our data. Variant chr7-27095697-ATGGTGGTGG-A is described in ClinVar as Benign. ClinVar VariationId is 587887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00354 (2864/808074) while in subpopulation SAS AF = 0.0485 (1238/25506). AF 95% confidence interval is 0.0463. There are 22 homozygotes in GnomAdExome4. There are 1658 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 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.207_215delCCACCACCA	p.His70_His72del	disruptive_inframe_deletion	Exon 1 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.207_215delCCACCACCA	p.His70_His72del	disruptive_inframe_deletion	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.207_215delCCACCACCA	p.His70_His72del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000494260.2	P49639-1
HOXA1	ENST00000355633.5	TSL:1	c.207_215delCCACCACCA	p.His70_His72del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000347851.5	E7ERT8
HOTAIRM1	ENST00000495032.1	TSL:5	n.26+41_26+49delTGGTGGTGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

260

AN:

141482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00348

Gnomad ASJ

AF:

0.0180

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0207

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.00467

GnomAD2 exomes

AF:

0.00364

AC:

846

AN:

232380

AF XY:

0.00408

show subpopulations

Gnomad AFR exome

AF:

0.000514

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.0000569

Gnomad FIN exome

AF:

0.0000507

Gnomad NFE exome

AF:

0.00139

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00354

AC:

2864

AN:

808074

Hom.:

AF XY:

0.00427

AC XY:

1658

AN XY:

388582

show subpopulations

African (AFR)

AF:

0.000916

AC:

AN:

25106

American (AMR)

AF:

0.00524

AC:

AN:

16414

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

323

AN:

12048

East Asian (EAS)

AF:

0.00

AC:

AN:

17096

South Asian (SAS)

AF:

0.0485

AC:

1238

AN:

25506

European-Finnish (FIN)

AF:

0.0000979

AC:

AN:

20436

Middle Eastern (MID)

AF:

0.0200

AC:

AN:

3402

European-Non Finnish (NFE)

AF:

0.00140

AC:

920

AN:

655828

Other (OTH)

AF:

0.00633

AC:

204

AN:

32238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

180

360

541

721

901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00183

AC:

259

AN:

141608

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

154

AN XY:

69194

show subpopulations

African (AFR)

AF:

0.000423

AC:

AN:

40230

American (AMR)

AF:

0.00348

AC:

AN:

14084

Ashkenazi Jewish (ASJ)

AF:

0.0180

AC:

AN:

3162

East Asian (EAS)

AF:

0.00

AC:

AN:

4656

South Asian (SAS)

AF:

0.0134

AC:

AN:

4262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9550

Middle Eastern (MID)

AF:

0.0224

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00102

AC:

AN:

62558

Other (OTH)

AF:

0.00462

AC:

AN:

1948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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.:

Bravo

AF:

0.00170

ClinVar

ClinVar submissions

Significance: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

6.2

Mutation Taster

=192/8

polymorphism

(source)

Splicing

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