7-27095689-GGGTGGCGAT-G

Variant names:

• chr7-27095689-GGGTGGCGAT-G
• rs544314279
• NM_005522.5:c.215_223delATCGCCACC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005522.5(HOXA1):​c.215_223delATCGCCACC​(p.His72_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 0.000694 in 1,613,002 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00069 (6 hom.)
• Consequence: HOXA1 NM_005522.5 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 2.13

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 7-27095689-GGGTGGCGAT-G is Benign according to our data. Variant chr7-27095689-GGGTGGCGAT-G is described in ClinVar as [Benign]. Clinvar id is 1205948.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-27095689-GGGTGGCGAT-G is described in Lovd as [Likely_benign]. Variant chr7-27095689-GGGTGGCGAT-G is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA1	NM_005522.5	c.215_223delATCGCCACC	p.His72_His74del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3	c.215_223delATCGCCACC	p.His72_His74del	disruptive_inframe_deletion	Exon 1 of 3		NP_705873.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460.2	c.215_223delATCGCCACC	p.His72_His74del	disruptive_inframe_deletion	Exon 1 of 2		NM_005522.5	ENSP00000494260.2
HOXA1	ENST00000355633.5	c.215_223delATCGCCACC	p.His72_His74del	disruptive_inframe_deletion	Exon 1 of 3	1		ENSP00000347851.5
HOTAIRM1	ENST00000495032.1	n.26+23_26+31delCGATGGTGG		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.000699 AC: 106 AN: 151628 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00152 AC: 379 AN: 250024 Hom.: 3 AF XY: 0.00143 AC XY: 193 AN XY: 135312

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0133

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000693 AC: 1013 AN: 1461254 Hom.: 6 AF XY: 0.000678 AC XY: 493 AN XY: 726950

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0133

Gnomad4 SAS exome AF: 0.00158

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000194

Gnomad4 OTH exome AF: 0.000845

GnomAD4 genome AF: 0.000699 AC: 106 AN: 151748 Hom.: 0 Cov.: 28 AF XY: 0.000849 AC XY: 63 AN XY: 74166

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000525

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.000629

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.0000844 Hom.: 0

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HOXA1: BS1, BS2 -

not specified Benign:1

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs544314279; hg19: chr7-27135308;