Variant chr16-172889-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000517.6(HBA2):c.-24C>G variant causes a 5 prime UTR 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 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.082 ( 1242 hom. )

Failed GnomAD Quality Control

Consequence

HBA2
NM_000517.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.42

Variant links:

Genes affected

HBA2 (HGNC:4824): (hemoglobin subunit alpha 2) 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]

HBA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-172889-C-G is Benign according to our data. Variant chr16-172889-C-G is described in ClinVar as [Benign]. Clinvar id is 439113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBA2	NM_000517.6 linkuse as main transcript	c.-24C>G		5_prime_UTR_variant	1/3	ENST00000251595.11	NP_000508.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
HBA2	ENST00000251595.11 linkuse as main transcript	c.-24C>G	5_prime_UTR_variant	1/3	1	NM_000517.6	ENSP00000251595	P1
HBA2	ENST00000482565.1 linkuse as main transcript		upstream_gene_variant		1
HBA2	ENST00000397806.1 linkuse as main transcript		upstream_gene_variant		2		ENSP00000380908

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

Gnomad AMR

AF:

0.00

Gnomad NFE

AF:

0.00

GnomAD3 exomes

AF:

0.0687

AC:

3594

AN:

52298

Hom.:

234

AF XY:

0.0707

AC XY:

1868

AN XY:

26412

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.0618

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.000387

Gnomad SAS exome

AF:

0.0898

Gnomad FIN exome

AF:

0.0696

Gnomad NFE exome

AF:

0.0968

Gnomad OTH exome

AF:

0.0995

GnomAD4 exome

AF:

0.0816

AC:

17551

AN:

215140

Hom.:

1242

Cov.:

AF XY:

0.0851

AC XY:

9799

AN XY:

115192

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.0578

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.000407

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.0513

Gnomad4 NFE exome

AF:

0.0866

Gnomad4 OTH exome

AF:

0.0794

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0351

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 21, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 31478238) -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Apr 05, 2023	- -

alpha Thalassemia

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, no assertion criteria provided	curation	The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	Nov 25, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.59

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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