rs7946748

chr11-5226496-G-Achr11-5226496-G-T

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.*60C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,277,896 control chromosomes in the GnomAD database, including 9,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (936 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8230 hom.)
• Consequence: HBB ENST00000485743.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.445

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=-0.81).
• BP6: Variant 11-5226496-G-A is Benign according to our data. Variant chr11-5226496-G-A is described in ClinVar as [Benign]. Clinvar id is 439774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-5226496-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBB	NM_000518.5	c.315+81C>T		intron_variant		ENST00000335295.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBB	ENST00000335295.4	c.315+81C>T		intron_variant		1	NM_000518.5	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16061 AN: 152074 Hom.: 933 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.116 AC: 130932 AN: 1125704 Hom.: 8230 Cov.: 15 AF XY: 0.119 AC XY: 68619 AN XY: 574284

Gnomad4 AFR exome AF: 0.0739

Gnomad4 AMR exome AF: 0.0668

Gnomad4 ASJ exome AF: 0.0929

Gnomad4 EAS exome AF: 0.0163

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.106 AC: 16062 AN: 152192 Hom.: 936 Cov.: 32 AF XY: 0.107 AC XY: 7997 AN XY: 74404

Gnomad4 AFR AF: 0.0788

Gnomad4 AMR AF: 0.0914

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.105

Alfa AF: 0.118 Hom.: 1083

Bravo AF: 0.0944

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

beta Thalassemia Benign:4

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, no assertion criteria provided	curation	The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	Nov 25, 2019	- -
Benign, no assertion criteria provided	research	College of Science, Al Muthanna University, Al Muthanna University	Jan 01, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
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	-0.81
Cadd	Benign	0.83
Dann	Benign	0.70

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: rs7946748; hg19: chr11-5247726;