ENST00000472694.1:n.153C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The ENST00000472694.1(HBA1):n.153C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 55 hom., cov: 28)

Exomes 𝑓: 0.0016 ( 56 hom. )

Failed GnomAD Quality Control

Consequence

HBA1
ENST00000472694.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.518

Publications

1 publications found

Variant links:

Genes affected

HBA1 (HGNC:4823): (hemoglobin subunit alpha 1) The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. These genes differ slightly over the 5' untranslated regions and the introns, but they differ significantly over the 3' untranslated regions. Two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. Alpha thalassemias result from deletions of each of the alpha genes as well as deletions of both HBA2 and HBA1; some nondeletion alpha thalassemias have also been reported. [provided by RefSeq, Jul 2008]

HBA1 Gene-Disease associations (from GenCC):

alpha thalassemia spectrum
Inheritance: AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
erythrocytosis, familial, 7
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
hemoglobin M disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Hb Bart's hydrops fetalis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hemoglobin H disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
methemoglobinemia, alpha type
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
Heinz body anemia
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HBA1 links:

ENSG00000294436 (HGNC:):

ENSG00000294436 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-176850-C-T is Benign according to our data. Variant chr16-176850-C-T is described in ClinVar as Benign. ClinVar VariationId is 439106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472694.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBA1	NM_000558.5	MANE Select	c.95+39C>T		intron	N/A	NP_000549.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HBA1	ENST00000472694.1	TSL:1	n.153C>T	non_coding_transcript_exon	Exon 1 of 2
HBA1	ENST00000320868.9	TSL:1 MANE Select	c.95+39C>T	intron	N/A	ENSP00000322421.5
HBA1	ENST00000487791.1	TSL:1	n.64+39C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2324

AN:

147906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00580

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000217

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000746

Gnomad OTH

AF:

0.00645

GnomAD2 exomes

AF:

0.00368

AC:

511

AN:

139020

AF XY:

0.00291

show subpopulations

Gnomad AFR exome

AF:

0.0654

Gnomad AMR exome

AF:

0.00282

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.000731

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00160

AC:

1912

AN:

1195586

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

828

AN XY:

597176

show subpopulations

African (AFR)

AF:

0.0596

AC:

1559

AN:

26152

American (AMR)

AF:

0.00319

AC:

113

AN:

35402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23848

East Asian (EAS)

AF:

0.00

AC:

AN:

34596

South Asian (SAS)

AF:

0.0000930

AC:

AN:

75244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47718

Middle Eastern (MID)

AF:

0.00137

AC:

AN:

3642

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

898118

Other (OTH)

AF:

0.00370

AC:

188

AN:

50866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

142

213

284

355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0158

AC:

2336

AN:

148026

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1066

AN XY:

72136

show subpopulations

African (AFR)

AF:

0.0566

AC:

2230

AN:

39376

American (AMR)

AF:

0.00579

AC:

AN:

15032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

4856

South Asian (SAS)

AF:

0.00

AC:

AN:

4612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000746

AC:

AN:

67056

Other (OTH)

AF:

0.00639

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

171

256

342

427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00117

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 16, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Dec 13, 2016

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

alpha Thalassemia

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.6

(source)

DANN

Benign

0.70

PhyloP100

0.52

PromoterAI

0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over