rs567259408

Variant names:

• chr11-5225367-A-G
• rs567259408
• ENST00000644706.1:n.95T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-5225367-A-G
• chr11-5225367-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The ENST00000644706.1(ENSG00000285498):​n.95T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 528,914 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (1 hom.)
• Consequence: ENSG00000285498 ENST00000644706.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.08

Genes affected

ENSG00000285498 (HGNC:):

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 -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-5225367-A-G is Benign according to our data. Variant chr11-5225367-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 256340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBB	NM_000518.5	c.*231T>C		downstream_gene_variant		ENST00000335295.4	NP_000509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285498	ENST00000644706.1	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 1
HBB	ENST00000335295.4	c.*231T>C		downstream_gene_variant		1	NM_000518.5	ENSP00000333994.3
HBB	ENST00000647020.1	c.*231T>C		downstream_gene_variant				ENSP00000494175.1
HBB	ENST00000633227.1	n.*491T>C		downstream_gene_variant		3		ENSP00000488004.1

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00159 AC: 600 AN: 376636 Hom.: 1 Cov.: 4 AF XY: 0.00144 AC XY: 291 AN XY: 201652

Gnomad4 AFR exome AF: 0.000280

Gnomad4 AMR exome AF: 0.00153

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00286

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.00122 AC XY: 91 AN XY: 74460

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000424 Hom.: 0

Bravo AF: 0.00128

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Apr 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.80
CADD	Benign	9.6
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs567259408; hg19: chr11-5246597;