11-5227540-G-A

Position:

• chr11-5227540-G-A

Variant summary

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

The ENST00000380315.2(HBB):​c.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 165,742 control chromosomes in the GnomAD database, including 75,920 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70092 hom., cov: 29)
  • Exomes 𝑓: 0.91 (5828 hom.)
• Consequence: HBB ENST00000380315.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.02

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=-0.84).
• BP6: Variant 11-5227540-G-A is Benign according to our data. Variant chr11-5227540-G-A is described in ClinVar as [Benign]. Clinvar id is 869330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-5227540-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBB	ENST00000380315.2	c.-47C>T		5_prime_UTR_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145258 AN: 151794 Hom.: 70043 Cov.: 29

Gnomad AFR AF: 0.974

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.951

GnomAD4 exome AF: 0.908 AC: 12555 AN: 13832 Hom.: 5828 Cov.: 0 AF XY: 0.905 AC XY: 6602 AN XY: 7292

Gnomad4 AFR exome AF: 0.968

Gnomad4 AMR exome AF: 0.814

Gnomad4 ASJ exome AF: 0.987

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.898

Gnomad4 FIN exome AF: 0.934

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.947

GnomAD4 genome AF: 0.957 AC: 145364 AN: 151910 Hom.: 70092 Cov.: 29 AF XY: 0.950 AC XY: 70562 AN XY: 74242

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.993

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.948

Alfa AF: 0.967 Hom.: 11575

Bravo AF: 0.947

Asia WGS AF: 0.761 AC: 2647 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

beta Thalassemia Benign:1

Benign, no assertion criteria provided

curation

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

Nov 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.062
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10742584; hg19: chr11-5248770;