rs16911905

Positions:

• chr11-5228060-G-C

Variant summary

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

The ENST00000380315.2(HBB):​c.-86-481C>G 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: HBB ENST00000380315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 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.-86-481C>G		intron_variant		5		ENSP00000369671

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.0480

Gnomad4 EAS AF: 0.0333

Gnomad4 SAS AF: 0.0892

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0825

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16911905; hg19: chr11-5249290;