rs7480526

Variant names:

• chr11-5226503-A-C
• rs7480526
• ENST00000485743.1:c.*53T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-5226503-A-C
• chr11-5226503-A-G
• chr11-5226503-A-T

Variant summary

Our verdict is Benign. The variant received -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:8
• Conservation: PhyloP100: 0.174
• Publications: 29 publications found

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 Gene-Disease associations (from GenCC):

• dominant beta-thalassemia

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• hemoglobin M disease

  Inheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen
• beta thalassemia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• beta-thalassemia HBB/LCRB

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• sickle cell disease and related diseases

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• erythrocytosis, familial, 6

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Heinz body anemia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• sickle cell disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• beta-thalassemia intermedia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• beta-thalassemia major

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• delta-beta-thalassemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin C disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin C-beta-thalassemia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin E disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin E-beta-thalassemia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-beta-thalassemia disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin c disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin d disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin E disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298932 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 439775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485743.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBB	NM_000518.5	MANE Select	c.315+74T>G		intron	N/A	NP_000509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBB	ENST00000485743.1	TSL:1	c.*53T>G		3_prime_UTR	Exon 2 of 2	ENSP00000496200.1
	HBB	ENST00000335295.4	TSL:1 MANE Select	c.315+74T>G		intron	N/A	ENSP00000333994.3
	HBB	ENST00000647020.1		c.315+74T>G		intron	N/A	ENSP00000494175.1

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

African (AFR) AF: 0.384 AC: 10831 AN: 28188

American (AMR) AF: 0.394 AC: 17003 AN: 43192

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 13403 AN: 24370

East Asian (EAS) AF: 0.181 AC: 6955 AN: 38356

South Asian (SAS) AF: 0.422 AC: 33955 AN: 80382

European-Finnish (FIN) AF: 0.469 AC: 24859 AN: 53032

Middle Eastern (MID) AF: 0.598 AC: 3118 AN: 5218

European-Non Finnish (NFE) AF: 0.478 AC: 413063 AN: 864772

Other (OTH) AF: 0.461 AC: 23762 AN: 51498

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

African (AFR) AF: 0.392 AC: 16250 AN: 41464

American (AMR) AF: 0.451 AC: 6879 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1899 AN: 3462

East Asian (EAS) AF: 0.173 AC: 894 AN: 5174

South Asian (SAS) AF: 0.410 AC: 1976 AN: 4820

European-Finnish (FIN) AF: 0.456 AC: 4820 AN: 10560

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32592 AN: 67986

Other (OTH) AF: 0.463 AC: 974 AN: 2104

Alfa AF: 0.410 Hom.: 3881

Bravo AF: 0.433

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	beta Thalassemia (4)
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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