rs1609812

Variant names:

• chr11-5225911-G-A
• rs1609812
• NM_000518.5:c.316-185C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5225911-G-A
• chr11-5225911-G-C

Variant summary

Our verdict is Benign. The variant received -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:9
• 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HBB	NM_000518.5	c.316-185C>T		intron_variant	Intron 2 of 2	ENST00000335295.4	NP_000509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBB	ENST00000335295.4	c.316-185C>T		intron_variant	Intron 2 of 2	1	NM_000518.5	ENSP00000333994.3
HBB	ENST00000647020.1	c.316-185C>T		intron_variant	Intron 2 of 2			ENSP00000494175.1
HBB	ENST00000475226.1	n.248-185C>T		intron_variant	Intron 1 of 1	2
HBB	ENST00000633227.1	n.*132-185C>T		intron_variant	Intron 2 of 2	3		ENSP00000488004.1

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 AC: 0.869267 AN: 0.869267

Gnomad4 AMR AF: 0.727 AC: 0.726904 AN: 0.726904

Gnomad4 ASJ AF: 0.864 AC: 0.863767 AN: 0.863767

Gnomad4 EAS AF: 0.495 AC: 0.494586 AN: 0.494586

Gnomad4 SAS AF: 0.625 AC: 0.625 AN: 0.625

Gnomad4 FIN AF: 0.787 AC: 0.787483 AN: 0.787483

Gnomad4 NFE AF: 0.841 AC: 0.840956 AN: 0.840956

Gnomad4 OTH AF: 0.819 AC: 0.818957 AN: 0.818957

Alfa AF: 0.829 Hom.: 74893

Bravo AF: 0.820

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

beta Thalassemia Benign:4

Nov 25, 2019

The ITHANET community portal, The Cyprus Institute of Neurology and Genetics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

- -

Jan 01, 2018

College of Science, Al Muthanna University, Al Muthanna University

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing;curation

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

May 15, 2015

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.37
DANN	Benign	0.11
Mutation Taster		=100/0	polymorphism (auto)

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;