7-27095697-ATGGTGGTGGTGG-ATGGTGG

Variant names:

• chr7-27095697-ATGGTGG-A
• rs747464910
• NM_005522.5:c.210_215delCCACCA

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_005522.5(HOXA1):​c.210_215delCCACCA​(p.His71_His72del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 949,670 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. H70H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: HOXA1 NM_005522.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.19
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005522.5
• BP6: Variant 7-27095697-ATGGTGG-A is Benign according to our data. Variant chr7-27095697-ATGGTGG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 588418.Status of the report is criteria_provided_single_submitter, 1 stars.

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.210_215delCCACCA	p.His71_His72del	disruptive_inframe_deletion	Exon 1 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.210_215delCCACCA	p.His71_His72del	disruptive_inframe_deletion	Exon 1 of 3	NP_705873.3	P49639-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA1	ENST00000643460.2	MANE Select	c.210_215delCCACCA	p.His71_His72del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000494260.2	P49639-1
	HOXA1	ENST00000355633.5	TSL:1	c.210_215delCCACCA	p.His71_His72del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000347851.5	E7ERT8
	HOTAIRM1	ENST00000495032.1	TSL:5	n.26+44_26+49delTGGTGG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 29 AN: 141484 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000284

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000283 AC: 229 AN: 808060 Hom.: 0 AF XY: 0.000283 AC XY: 110 AN XY: 388576

African (AFR) AF: 0.000398 AC: 10 AN: 25106

American (AMR) AF: 0.000548 AC: 9 AN: 16414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12048

East Asian (EAS) AF: 0.00 AC: 0 AN: 17096

South Asian (SAS) AF: 0.000118 AC: 3 AN: 25506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20430

Middle Eastern (MID) AF: 0.00176 AC: 6 AN: 3402

European-Non Finnish (NFE) AF: 0.000287 AC: 188 AN: 655822

Other (OTH) AF: 0.000403 AC: 13 AN: 32236

GnomAD4 genome AF: 0.000205 AC: 29 AN: 141610 Hom.: 0 Cov.: 30 AF XY: 0.000145 AC XY: 10 AN XY: 69196

African (AFR) AF: 0.000348 AC: 14 AN: 40230

American (AMR) AF: 0.000284 AC: 4 AN: 14084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3162

East Asian (EAS) AF: 0.00 AC: 0 AN: 4656

South Asian (SAS) AF: 0.00 AC: 0 AN: 4264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.000176 AC: 11 AN: 62558

Other (OTH) AF: 0.00 AC: 0 AN: 1948

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000147

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=149/51	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs747464910; hg19: chr7-27135316; COSMIC: COSV106093192; COSMIC: COSV106093192;