Variant rs7480526 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000485743(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 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.174

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]

HBB links:

HBB (HGNC:):

HBB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
HBB	NM_000518.5 linkuse as main transcript	c.315+74T>G		intron_variant		ENST00000335295.4	NP_000509.1	P68871D9YZU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBB	ENST00000335295.4 linkuse as main transcript	c.315+74T>G		intron_variant		1	NM_000518.5	ENSP00000333994.3		P68871

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66703

AN:

151910

Hom.:

15079

Cov.:

show subpopulations

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.:

AF XY:

0.460

AC XY:

278095

AN XY:

603938

show subpopulations

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.:

AF XY:

0.437

AC XY:

32464

AN XY:

74316

show subpopulations

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

beta Thalassemia

Benign:3

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	- -
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

-0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over