Genetic Variant HOXA1:p.Arg73_His74del (chr7-27095691-GTGGCGA-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_005522.5(HOXA1):c.216_221delTCGCCA(p.Arg73_His74del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,544,470 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00044 ( 4 hom. )

Consequence

HOXA1
NM_005522.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.13

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 made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 7-27095691-GTGGCGA-G is Benign according to our data. Variant chr7-27095691-GTGGCGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 3051297.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA1	NM_005522.5 link	c.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000643460.2	NP_005513.2	P49639
HOXA1	NM_153620.3 link	c.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	Exon 1 of 3		NP_705873.3	P49639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HOXA1	ENST00000643460.2 link	c.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	Exon 1 of 2		NM_005522.5	ENSP00000494260.2	A0A2R8Y4R9
HOXA1	ENST00000355633.5 link	c.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	Exon 1 of 3	1		ENSP00000347851.5	E7ERT8
HOTAIRM1	ENST00000495032.1 link	n.26+23_26+28delCGATGG		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.000442

AC:

AN:

149486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000583

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.000295

Gnomad EAS

AF:

0.000209

Gnomad SAS

AF:

0.00193

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000404

Gnomad OTH

AF:

0.000488

GnomAD3 exomes

AF:

0.000507

AC:

126

AN:

248578

Hom.:

AF XY:

0.000684

AC XY:

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00200

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000332

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.000440

AC:

614

AN:

1394864

Hom.:

AF XY:

0.000503

AC XY:

350

AN XY:

695830

show subpopulations

Gnomad4 AFR exome

AF:

0.000513

Gnomad4 AMR exome

AF:

0.000181

Gnomad4 ASJ exome

AF:

0.000117

Gnomad4 EAS exome

AF:

0.000158

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.0000769

Gnomad4 NFE exome

AF:

0.000320

Gnomad4 OTH exome

AF:

0.000516

GnomAD4 genome

AF:

0.000441

AC:

AN:

149606

Hom.:

Cov.:

AF XY:

0.000480

AC XY:

AN XY:

72968

show subpopulations

Gnomad4 AFR

AF:

0.000582

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.000295

Gnomad4 EAS

AF:

0.000209

Gnomad4 SAS

AF:

0.00193

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000404

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.000434

Hom.:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000475

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HOXA1-related disorder

Benign:1

Jul 30, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over