11-5226942-TCAC-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting

The NM_000518.5(HBB):​c.77_79del​(p.Gly26del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars). Synonymous variant affecting the same amino acid position (i.e. G26G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

HBB
NM_000518.5 inframe_deletion

Scores

Not classified

Clinical Significance

other no assertion criteria provided O:2

Conservation

PhyloP100: 1.15
Variant links:
Genes affected
HBB (HGNC:4827): (hemoglobin subunit beta) The alpha (HBA) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, Hb A. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains. Mutant beta globin causes sickle cell anemia. Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1
In a hotspot region, there are 10 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 3 benign, 17 uncertain in NM_000518.5
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000518.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HBBNM_000518.5 linkuse as main transcriptc.77_79del p.Gly26del inframe_deletion 1/3 ENST00000335295.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HBBENST00000335295.4 linkuse as main transcriptc.77_79del p.Gly26del inframe_deletion 1/31 NM_000518.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: other
Submissions summary: Other:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

HEMOGLOBIN HT Other:1
other, no assertion criteria providedliterature onlyOMIMDec 12, 2017- -
HEMOGLOBIN HIGASHITOCHIGI Other:1
other, no assertion criteria providedliterature onlyOMIMDec 12, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.31
Position offset: 7

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.

Other links and lift over

dbSNP: rs63749918; hg19: chr11-5248172; API