rs11036364

Positions:

• chr11-5227774-A-G
• chr11-5227774-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000380315.2(HBB):​c.-86-195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,862 control chromosomes in the GnomAD database, including 14,957 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 0.44 (14957 hom., cov: 31)
• Consequence: HBB ENST00000380315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBB	ENST00000380315.2	c.-86-195T>C		intron_variant		5		ENSP00000369671

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66343 AN: 151742 Hom.: 14932 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.437 AC: 66412 AN: 151862 Hom.: 14957 Cov.: 31 AF XY: 0.434 AC XY: 32203 AN XY: 74208

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.445

Alfa AF: 0.485 Hom.: 23590

Bravo AF: 0.431

Asia WGS AF: 0.398 AC: 1386 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11036364; hg19: chr11-5249004;