rs35672478

chr16-177018-AGGT-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4_Supporting PP5

The NM_000558.5(HBA1):c.188_190del(p.Val63del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Pathogenic,other (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HBA1 NM_000558.5 inframe_deletion
• Clinical Significance: Pathogenic; other no assertion criteria provided P:2 O:1
• Conservation: PhyloP100: 5.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000558.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 16-177018-AGGT-A is Pathogenic according to our data. Variant chr16-177018-AGGT-A is described in ClinVar as [Pathogenic, other]. Clinvar id is 15875.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBA1	NM_000558.5	c.188_190del	p.Val63del	inframe_deletion	2/3	ENST00000320868.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBA1	ENST00000320868.9	c.188_190del	p.Val63del	inframe_deletion	2/3	1	NM_000558.5	P1
HBA1	ENST00000472694.1	n.324_326del		non_coding_transcript_exon_variant	1/2	1
HBA1	ENST00000487791.1	n.157_159del		non_coding_transcript_exon_variant	2/2	1
HBA1	ENST00000397797.1	c.92_94del	p.Val31del	inframe_deletion	2/3	2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic; other

Submissions summary: Pathogenic:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

alpha Thalassemia Pathogenic:1

Pathogenic, no assertion criteria provided

curation

The ITHANET community portal, The Cyprus Institute of Neurology and Genetics

Nov 25, 2019

- -

Hemoglobin H disease, nondeletional Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 1999

- -

HEMOGLOBIN AGHIA SOPHIA Other:1

other, no assertion criteria provided

literature only

OMIM

Jul 20, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs35672478; hg19: chr16-227017;