rs7480526

chr11-5226503-A-Cchr11-5226503-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000485743.1(HBB):c.*53T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,341,036 control chromosomes in the GnomAD database, including 143,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15086 hom., cov: 32)
  • Exomes 𝑓: 0.46 (128805 hom.)
• Consequence: HBB ENST00000485743.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.174

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-5226503-A-C is Benign according to our data. Variant chr11-5226503-A-C is described in ClinVar as [Benign]. Clinvar id is 439775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-5226503-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBB	NM_000518.5	c.315+74T>G		intron_variant		ENST00000335295.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBB	ENST00000335295.4	c.315+74T>G		intron_variant		1	NM_000518.5	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66703 AN: 151910 Hom.: 15079 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.460 AC: 546949 AN: 1189008 Hom.: 128805 Cov.: 17 AF XY: 0.460 AC XY: 278095 AN XY: 603938

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.550

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.478

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.439 AC: 66749 AN: 152028 Hom.: 15086 Cov.: 32 AF XY: 0.437 AC XY: 32464 AN XY: 74316

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.463

Alfa AF: 0.372 Hom.: 1427

Bravo AF: 0.433

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

beta Thalassemia Benign:3

Benign, no assertion criteria provided	curation	The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	Nov 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.1
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs7480526; hg19: chr11-5247733; COSMIC: COSV58942465; COSMIC: COSV58942465;