11-5225245-C-T

Variant names:

• chr11-5225245-C-T
• rs112988270
• ENST00000644706.1:n.217G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000644706.1(ENSG00000285498):​n.217G>A 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 0.01 in 348,168 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (7 hom., cov: 32)
  • Exomes 𝑓: 0.012 (35 hom.)
• Consequence: ENSG00000285498 ENST00000644706.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-5225245-C-T is Benign according to our data. Variant chr11-5225245-C-T is described in ClinVar as [Benign]. Clinvar id is 256343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00697 (1061/152268) while in subpopulation SAS AF= 0.0382 (184/4814). AF 95% confidence interval is 0.0337. There are 7 homozygotes in gnomad4. There are 521 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBB	NM_000518.5	c.*353G>A		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.217G>A		non_coding_transcript_exon_variant	Exon 1 of 1
HBB	ENST00000335295.4	c.*353G>A		downstream_gene_variant		1	NM_000518.5	ENSP00000333994.3
HBB	ENST00000647020.1	c.*353G>A		downstream_gene_variant				ENSP00000494175.1
HBB	ENST00000633227.1	n.*613G>A		downstream_gene_variant		3		ENSP00000488004.1

Frequencies

GnomAD3 genomes AF: 0.00695 AC: 1058 AN: 152150 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00881

Gnomad OTH AF: 0.00910

GnomAD4 exome AF: 0.0124 AC: 2423 AN: 195900 Hom.: 35 Cov.: 0 AF XY: 0.0147 AC XY: 1566 AN XY: 106424

Gnomad4 AFR exome AF: 0.00109

Gnomad4 AMR exome AF: 0.00532

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.000366

Gnomad4 SAS exome AF: 0.0313

Gnomad4 FIN exome AF: 0.00294

Gnomad4 NFE exome AF: 0.00861

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.00697 AC: 1061 AN: 152268 Hom.: 7 Cov.: 32 AF XY: 0.00700 AC XY: 521 AN XY: 74450

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00881

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00310 Hom.: 1

Bravo AF: 0.00612

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

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	-0.80
CADD	Benign	0.91
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112988270; hg19: chr11-5246475;