NM_005522.5:c.213C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005522.5(HOXA1):c.213C>T(p.His71His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,092,248 control chromosomes in the GnomAD database, including 810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 61 hom., cov: 30)

Exomes 𝑓: 0.049 ( 749 hom. )

Consequence

HOXA1
NM_005522.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.195

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 7-27095700-G-A is Benign according to our data. Variant chr7-27095700-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 359966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-27095700-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.195 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA1	NM_005522.5 link	c.213C>T	p.His71His	synonymous_variant	Exon 1 of 2	ENST00000643460.2	NP_005513.2	P49639
HOXA1	NM_153620.3 link	c.213C>T	p.His71His	synonymous_variant	Exon 1 of 3		NP_705873.3	P49639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HOXA1	ENST00000643460.2 link	c.213C>T	p.His71His	synonymous_variant	Exon 1 of 2		NM_005522.5	ENSP00000494260.2	A0A2R8Y4R9
HOXA1	ENST00000355633.5 link	c.213C>T	p.His71His	synonymous_variant	Exon 1 of 3	1		ENSP00000347851.5	E7ERT8
HOTAIRM1	ENST00000495032.1 link	n.26+28G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3606

AN:

150004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00660

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.0442

Gnomad EAS

AF:

0.000784

Gnomad SAS

AF:

0.0194

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0333

Gnomad NFE

AF:

0.0343

Gnomad OTH

AF:

0.0317

GnomAD3 exomes

AF:

0.0302

AC:

6222

AN:

206014

Hom.:

106

AF XY:

0.0312

AC XY:

3445

AN XY:

110490

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.0257

Gnomad ASJ exome

AF:

0.0584

Gnomad EAS exome

AF:

0.00107

Gnomad SAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.0293

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0345

GnomAD4 exome

AF:

0.0493

AC:

46489

AN:

942132

Hom.:

749

Cov.:

AF XY:

0.0504

AC XY:

23000

AN XY:

456538

show subpopulations

Gnomad4 AFR exome

AF:

0.00747

Gnomad4 AMR exome

AF:

0.0461

Gnomad4 ASJ exome

AF:

0.0753

Gnomad4 EAS exome

AF:

0.00138

Gnomad4 SAS exome

AF:

0.0471

Gnomad4 FIN exome

AF:

0.0513

Gnomad4 NFE exome

AF:

0.0516

Gnomad4 OTH exome

AF:

0.0492

GnomAD4 genome

AF:

0.0240

AC:

3606

AN:

150116

Hom.:

Cov.:

AF XY:

0.0237

AC XY:

1739

AN XY:

73272

show subpopulations

Gnomad4 AFR

AF:

0.00658

Gnomad4 AMR

AF:

0.0306

Gnomad4 ASJ

AF:

0.0442

Gnomad4 EAS

AF:

0.000786

Gnomad4 SAS

AF:

0.0194

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.0343

Gnomad4 OTH

AF:

0.0314

Alfa

AF:

0.0198

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

HOXA1-related disorder

Benign:1

Jun 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Mar 13, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as 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. -

Human HOXA1 syndromes

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bosley-Salih-Alorainy syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bilateral microtia-deafness-cleft palate syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.6

DANN

Benign

0.94

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