rs34698907

Positions:

• chr11-5249731-CCAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_000559.3(HBG1):​c.71_73delCTG​(p.Ala24del) variant causes a disruptive inframe deletion change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 4)
• Consequence: HBG1 NM_000559.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83

Genes affected

HBG1 (HGNC:4831): (hemoglobin subunit gamma 1) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

ENSG00000284931 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000559.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBG1	NM_000559.3	c.71_73delCTG	p.Ala24del	disruptive_inframe_deletion	1/3	ENST00000330597.5	NP_000550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBG1	ENST00000330597.5	c.71_73delCTG	p.Ala24del	disruptive_inframe_deletion	1/3	1	NM_000559.3	ENSP00000327431.4
ENSG00000284931	ENST00000642908.1	c.316-1247_316-1245delCTG		intron_variant				ENSP00000495346.1

Frequencies

GnomAD3 genomes Cov.: 4

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

GnomAD4 genome Cov.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs34698907; hg19: chr11-5270961;