Variant 7-27095694-GCGA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_005522.5(HOXA1):c.216_218del(p.Arg73del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,302,078 control chromosomes in the GnomAD database, including 824 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.025 ( 61 hom., cov: 28)

Exomes 𝑓: 0.041 ( 763 hom. )

Consequence

HOXA1
NM_005522.5 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 7-27095694-GCGA-G is Benign according to our data. Variant chr7-27095694-GCGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 369584.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-27095694-GCGA-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0245 (3616/147328) while in subpopulation NFE AF= 0.0351 (2314/65910). AF 95% confidence interval is 0.0339. There are 61 homozygotes in gnomad4. There are 1742 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA1	NM_005522.5 linkuse as main transcript	c.216_218del	p.Arg73del	inframe_deletion	1/2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3 linkuse as main transcript	c.216_218del	p.Arg73del	inframe_deletion	1/3		NP_705873.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HOXA1	ENST00000643460.2 linkuse as main transcript	c.216_218del	p.Arg73del	inframe_deletion	1/2		NM_005522.5	ENSP00000494260	P1
HOXA1	ENST00000355633.5 linkuse as main transcript	c.216_218del	p.Arg73del	inframe_deletion	1/3	1		ENSP00000347851
HOTAIRM1	ENST00000495032.1 linkuse as main transcript	n.26+23_26+25del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3616

AN:

147212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0442

Gnomad EAS

AF:

0.000850

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0251

Gnomad MID

AF:

0.0329

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0321

GnomAD4 exome

AF:

0.0405

AC:

46772

AN:

1154750

Hom.:

763

AF XY:

0.0403

AC XY:

23126

AN XY:

574534

show subpopulations

Gnomad4 AFR exome

AF:

0.00607

Gnomad4 AMR exome

AF:

0.0270

Gnomad4 ASJ exome

AF:

0.0539

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.0245

Gnomad4 FIN exome

AF:

0.0316

Gnomad4 NFE exome

AF:

0.0451

Gnomad4 OTH exome

AF:

0.0380

GnomAD4 genome

AF:

0.0245

AC:

3616

AN:

147328

Hom.:

Cov.:

AF XY:

0.0243

AC XY:

1742

AN XY:

71826

show subpopulations

Gnomad4 AFR

AF:

0.00670

Gnomad4 AMR

AF:

0.0309

Gnomad4 ASJ

AF:

0.0442

Gnomad4 EAS

AF:

0.000852

Gnomad4 SAS

AF:

0.0198

Gnomad4 FIN

AF:

0.0251

Gnomad4 NFE

AF:

0.0351

Gnomad4 OTH

AF:

0.0318

Alfa

AF:

0.0248

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Bilateral microtia-deafness-cleft palate syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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