rs558554234

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_000518.5(HBB):​c.316-238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 152,242 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 2 hom., cov: 32)

Consequence

HBB
NM_000518.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: -0.598
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BS2
High Homozygotes in GnomAd4 at 2 SD geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HBBNM_000518.5 linkuse as main transcriptc.316-238C>T intron_variant ENST00000335295.4 NP_000509.1 P68871D9YZU5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HBBENST00000335295.4 linkuse as main transcriptc.316-238C>T intron_variant 1 NM_000518.5 ENSP00000333994.3 P68871
HBBENST00000647020.1 linkuse as main transcriptc.316-238C>T intron_variant ENSP00000494175.1 P68871
HBBENST00000475226.1 linkuse as main transcriptn.248-238C>T intron_variant 2
HBBENST00000633227.1 linkuse as main transcriptn.*132-238C>T intron_variant 3 ENSP00000488004.1 A0A0J9YWK4

Frequencies

GnomAD3 genomes
AF:
0.000526
AC:
80
AN:
152124
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0164
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000525
AC:
80
AN:
152242
Hom.:
2
Cov.:
32
AF XY:
0.000658
AC XY:
49
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0164
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000693
Hom.:
0
Bravo
AF:
0.000117
Asia WGS
AF:
0.00491
AC:
17
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Pathogenic:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesAug 08, 2023- -
beta Thalassemia Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyHb Lab, Kinderklinik Ulm, University Hospital UlmMar 08, 2018Rare thalassemic variant that could cause severe Thalassemia (Major or intermedia) when associated with other more common beta0 thalassemic alleles. -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.52
DANN
Benign
0.30

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.

Other links and lift over

dbSNP: rs558554234; hg19: chr11-5247194; API