rs10742583

Positions:

• chr11-5227411-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000380315.2(HBB):​c.-19+101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 279,618 control chromosomes in the GnomAD database, including 89,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51722 hom., cov: 31)
  • Exomes 𝑓: 0.77 (38161 hom.)
• Consequence: HBB ENST00000380315.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.0930

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-5227411-G-A is Benign according to our data. Variant chr11-5227411-G-A is described in ClinVar as [Benign]. Clinvar id is 869329.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-5227411-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.5227411G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBB	ENST00000380315.2	c.-19+101C>T		intron_variant		5		ENSP00000369671.2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124630 AN: 152036 Hom.: 51690 Cov.: 31

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.766 AC: 97584 AN: 127464 Hom.: 38161 AF XY: 0.748 AC XY: 50260 AN XY: 67156

Gnomad4 AFR exome AF: 0.879

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.772

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 0.796

GnomAD4 genome AF: 0.820 AC: 124719 AN: 152154 Hom.: 51722 Cov.: 31 AF XY: 0.811 AC XY: 60328 AN XY: 74380

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.824

Alfa AF: 0.823 Hom.: 9363

Bravo AF: 0.824

Asia WGS AF: 0.580 AC: 2020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

beta Thalassemia Benign:1

Benign, no assertion criteria provided

curation

The ITHANET community portal, The Cyprus Institute of Neurology and Genetics

Nov 25, 2019

- -

not provided Benign:1

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	-0.84
CADD	Benign	0.20
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10742583; hg19: chr11-5248641;