7-27095697-ATGG-A

Position:

chr7-27095697-ATGG-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_005522.5(HOXA1):c.213_215delCCA(p.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 0.00112 in 943,574 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. H71H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

HOXA1
NM_005522.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 7-27095697-ATGG-A is Benign according to our data. Variant chr7-27095697-ATGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 588087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-27095697-ATGG-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA1	NM_005522.5 link	c.213_215delCCA	p.His72del	disruptive_inframe_deletion	1/2	ENST00000643460.2	NP_005513.2	P49639
HOXA1	NM_153620.3 link	c.213_215delCCA	p.His72del	disruptive_inframe_deletion	1/3		NP_705873.3	P49639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HOXA1	ENST00000643460.2 link	c.213_215delCCA	p.His72del	disruptive_inframe_deletion	1/2		NM_005522.5	ENSP00000494260.2	A0A2R8Y4R9
HOXA1	ENST00000355633.5 link	c.213_215delCCA	p.His72del	disruptive_inframe_deletion	1/3	1		ENSP00000347851.5	E7ERT8
HOTAIRM1	ENST00000495032.1 link	n.26+47_26+49delTGG		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

170

AN:

141466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00192

Gnomad ASJ

AF:

0.00127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000940

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000639

Gnomad OTH

AF:

0.00207

GnomAD3 exomes

AF:

0.000783

AC:

182

AN:

232380

Hom.:

AF XY:

0.000803

AC XY:

101

AN XY:

125726

show subpopulations

Gnomad AFR exome

AF:

0.00263

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.000549

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000101

Gnomad NFE exome

AF:

0.000736

Gnomad OTH exome

AF:

0.000701

GnomAD4 exome

AF:

0.00110

AC:

885

AN:

801982

Hom.:

AF XY:

0.00118

AC XY:

454

AN XY:

385670

show subpopulations

Gnomad4 AFR exome

AF:

0.00235

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.000835

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.000297

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00121

AC:

171

AN:

141592

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

69190

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00192

Gnomad4 ASJ

AF:

0.00127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000938

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000655

Gnomad4 OTH

AF:

0.00205

Bravo

AF:

0.00126

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 13, 2019

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 25, 2018

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

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