rs1609812

chr11-5225911-G-Achr11-5225911-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000518.5(HBB):c.316-185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,150 control chromosomes in the GnomAD database, including 51,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.82 (51216 hom., cov: 32)
• Consequence: HBB NM_000518.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.59

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-5225911-G-A is Benign according to our data. Variant chr11-5225911-G-A is described in ClinVar as [Benign]. Clinvar id is 36316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-5225911-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBB	NM_000518.5	c.316-185C>T		intron_variant		ENST00000335295.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBB	ENST00000335295.4	c.316-185C>T		intron_variant		1	NM_000518.5	P1
HBB	ENST00000647020.1	c.316-185C>T		intron_variant				P1
HBB	ENST00000633227.1	c.*132-185C>T		intron_variant, NMD_transcript_variant		3
HBB	ENST00000475226.1	n.248-185C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124056 AN: 152032 Hom.: 51185 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.816 AC: 124145 AN: 152150 Hom.: 51216 Cov.: 32 AF XY: 0.807 AC XY: 60043 AN XY: 74374

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.819

Alfa AF: 0.831 Hom.: 51869

Bravo AF: 0.820

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

beta Thalassemia Benign:4

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, no assertion criteria provided	curation	The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	Nov 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing;curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -
Benign, no assertion criteria provided	research	College of Science, Al Muthanna University, Al Muthanna University	Jan 01, 2018	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 15, 2015	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.37
Dann	Benign	0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs1609812; hg19: chr11-5247141;