rs7946748

Variant names:

• chr11-5226496-G-A
• rs7946748
• ENST00000485743.1:c.*60C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5226496-G-A
• chr11-5226496-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000485743.1(HBB):​c.*60C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,277,896 control chromosomes in the GnomAD database, including 9,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (936 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8230 hom.)
• Consequence: HBB ENST00000485743.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.445
• Publications: 15 publications found

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]

HBB Gene-Disease associations (from GenCC):

• dominant beta-thalassemia

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• erythrocytosis, familial, 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• hemoglobin M disease

  Inheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet
• unstable hemoglobin disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• beta thalassemia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• beta-thalassemia HBB/LCRB

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• sickle cell disease and related diseases

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Heinz body anemia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• sickle cell disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• beta-thalassemia intermedia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• beta-thalassemia major

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• delta-beta-thalassemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin C disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin C-beta-thalassemia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin E disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemoglobin E-beta-thalassemia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-beta-thalassemia disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin c disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin d disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sickle cell-hemoglobin E disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298932 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-5226496-G-A is Benign according to our data. Variant chr11-5226496-G-A is described in ClinVar as Benign. ClinVar VariationId is 439774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485743.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBB	NM_000518.5	MANE Select	c.315+81C>T		intron	N/A	NP_000509.1	D9YZU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBB	ENST00000485743.1	TSL:1	c.*60C>T		3_prime_UTR	Exon 2 of 2	ENSP00000496200.1	A0A2R8Y7R2
	HBB	ENST00000335295.4	TSL:1 MANE Select	c.315+81C>T		intron	N/A	ENSP00000333994.3	P68871
	HBB	ENST00000647020.1		c.315+81C>T		intron	N/A	ENSP00000494175.1	P68871

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16061 AN: 152074 Hom.: 933 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.116 AC: 130932 AN: 1125704 Hom.: 8230 Cov.: 15 AF XY: 0.119 AC XY: 68619 AN XY: 574284

African (AFR) AF: 0.0739 AC: 2002 AN: 27080

American (AMR) AF: 0.0668 AC: 2851 AN: 42656

Ashkenazi Jewish (ASJ) AF: 0.0929 AC: 2221 AN: 23896

East Asian (EAS) AF: 0.0163 AC: 619 AN: 38032

South Asian (SAS) AF: 0.174 AC: 13733 AN: 78718

European-Finnish (FIN) AF: 0.145 AC: 7670 AN: 52754

Middle Eastern (MID) AF: 0.103 AC: 526 AN: 5084

European-Non Finnish (NFE) AF: 0.119 AC: 95809 AN: 808090

Other (OTH) AF: 0.111 AC: 5501 AN: 49394

GnomAD4 genome AF: 0.106 AC: 16062 AN: 152192 Hom.: 936 Cov.: 32 AF XY: 0.107 AC XY: 7997 AN XY: 74404

African (AFR) AF: 0.0788 AC: 3271 AN: 41528

American (AMR) AF: 0.0914 AC: 1397 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5182

South Asian (SAS) AF: 0.170 AC: 822 AN: 4826

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10568

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8278 AN: 68012

Other (OTH) AF: 0.105 AC: 221 AN: 2112

Alfa AF: 0.115 Hom.: 2587

Bravo AF: 0.0944

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	beta Thalassemia (4)
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.83
DANN	Benign	0.70
PhyloP100		-0.45
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

Other links and lift over

dbSNP: rs7946748; hg19: chr11-5247726;