7-27095697-ATGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGG

Variant names:

• chr7-27095697-A-ATGGTGGTGG
• rs747464910
• NM_005522.5:c.207_215dupCCACCACCA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005522.5(HOXA1):​c.207_215dupCCACCACCA​(p.His70_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 0.000304 in 141,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00067 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXA1 NM_005522.5 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59

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 -2 ACMG points.

• BP6: Variant 7-27095697-A-ATGGTGGTGG is Benign according to our data. Variant chr7-27095697-A-ATGGTGGTGG is described in ClinVar as [Likely_benign]. Clinvar id is 587896.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA1	NM_005522.5	c.207_215dupCCACCACCA	p.His70_His72dup	disruptive_inframe_insertion	Exon 1 of 2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3	c.207_215dupCCACCACCA	p.His70_His72dup	disruptive_inframe_insertion	Exon 1 of 3		NP_705873.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460.2	c.207_215dupCCACCACCA	p.His70_His72dup	disruptive_inframe_insertion	Exon 1 of 2		NM_005522.5	ENSP00000494260.2
HOXA1	ENST00000355633.5	c.207_215dupCCACCACCA	p.His70_His72dup	disruptive_inframe_insertion	Exon 1 of 3	1		ENSP00000347851.5
HOTAIRM1	ENST00000495032.1	n.26+41_26+49dupTGGTGGTGG		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.000304 AC: 43 AN: 141484 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000997

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000711

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00846

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000320

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000818 AC: 190 AN: 232380 Hom.: 1 AF XY: 0.00117 AC XY: 147 AN XY: 125726

Gnomad AFR exome AF: 0.000193

Gnomad AMR exome AF: 0.0000615

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000171

Gnomad SAS exome AF: 0.00590

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000872

Gnomad OTH exome AF: 0.000351

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000668 AC: 540 AN: 808064 Hom.: 2 Cov.: 52 AF XY: 0.00102 AC XY: 395 AN XY: 388578

Gnomad4 AFR exome AF: 0.000199

Gnomad4 AMR exome AF: 0.000183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000292

Gnomad4 SAS exome AF: 0.0176

Gnomad4 FIN exome AF: 0.0000489

Gnomad4 NFE exome AF: 0.0000930

Gnomad4 OTH exome AF: 0.000465

GnomAD4 genome AF: 0.000304 AC: 43 AN: 141610 Hom.: 0 Cov.: 30 AF XY: 0.000448 AC XY: 31 AN XY: 69196

Gnomad4 AFR AF: 0.0000994

Gnomad4 AMR AF: 0.0000710

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00844

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000320

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Nov 30, 2017

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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: rs747464910; hg19: chr7-27135316;