7-27095697-A-ATGGTGGTGG

Variant summary

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

The NM_005522.5(HOXA1):​c.215_216insCCACCACCA​(p.His70_His72dup) variant causes a 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 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
HOXA1NM_005522.5 linkuse as main transcriptc.215_216insCCACCACCA p.His70_His72dup inframe_insertion 1/2 ENST00000643460.2 NP_005513.2
HOXA1NM_153620.3 linkuse as main transcriptc.215_216insCCACCACCA p.His70_His72dup inframe_insertion 1/3 NP_705873.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HOXA1ENST00000643460.2 linkuse as main transcriptc.215_216insCCACCACCA p.His70_His72dup inframe_insertion 1/2 NM_005522.5 ENSP00000494260 P1
HOXA1ENST00000355633.5 linkuse as main transcriptc.215_216insCCACCACCA p.His70_His72dup inframe_insertion 1/31 ENSP00000347851
HOTAIRM1ENST00000495032.1 linkuse as main transcriptn.26+41_26+49dup intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.000304
AC:
43
AN:
141484
Hom.:
0
Cov.:
30
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 30, 2017This 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

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.

Other links and lift over

dbSNP: rs747464910; hg19: chr7-27135316; API