chr11-5228060-G-C

Variant names:

• chr11-5228060-G-C
• rs16911905
• ENST00000380315.2:c.-86-481C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000759072.1(ENSG00000298932):​n.265+2332G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 151,958 control chromosomes in the GnomAD database, including 1,220 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1220 hom., cov: 32)
• Consequence: ENSG00000298932 ENST00000759072.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• Publications: 7 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• erythrocytosis, familial, 6

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

  Inheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet
• unstable hemoglobin disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: 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), Ambry Genetics, ClinGen
• sickle cell disease and related diseases

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Heinz body anemia

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

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000759072.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBB	ENST00000380315.2	TSL:5	c.-86-481C>G		intron	N/A	ENSP00000369671.2	F8W6P5
	ENSG00000298932	ENST00000759072.1		n.265+2332G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15425 AN: 151840 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0480

Gnomad EAS AF: 0.0338

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0795

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15463 AN: 151958 Hom.: 1220 Cov.: 32 AF XY: 0.0984 AC XY: 7315 AN XY: 74308

African (AFR) AF: 0.226 AC: 9367 AN: 41380

American (AMR) AF: 0.0532 AC: 813 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0480 AC: 166 AN: 3460

East Asian (EAS) AF: 0.0333 AC: 172 AN: 5162

South Asian (SAS) AF: 0.0892 AC: 429 AN: 4812

European-Finnish (FIN) AF: 0.0432 AC: 458 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3830 AN: 67962

Other (OTH) AF: 0.0825 AC: 174 AN: 2110

Alfa AF: 0.0810 Hom.: 101

Bravo AF: 0.115

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.41
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16911905; hg19: chr11-5249290;