rs7936823

Positions:

• chr11-5228938-G-A

Variant summary

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

The ENST00000380315.2(HBB):​c.-87+314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,006 control chromosomes in the GnomAD database, including 23,700 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 0.55 (23700 hom., cov: 33)
• Consequence: HBB ENST00000380315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.5228938G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBB	ENST00000380315.2	c.-87+314C>T		intron_variant		5		ENSP00000369671.2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82963 AN: 151888 Hom.: 23653 Cov.: 33

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.547 AC: 83073 AN: 152006 Hom.: 23700 Cov.: 33 AF XY: 0.548 AC XY: 40753 AN XY: 74302

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.573

Alfa AF: 0.497 Hom.: 2406

Bravo AF: 0.562

Asia WGS AF: 0.616 AC: 2142 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7936823; hg19: chr11-5250168;