rs3813727

Positions:

• chr11-5234682-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000643122.1(HBD):​c.-28-221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 534,640 control chromosomes in the GnomAD database, including 62,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14996 hom., cov: 32)
  • Exomes 𝑓: 0.49 (47739 hom.)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.778

Genes affected

HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-5234682-A-G is Benign according to our data. Variant chr11-5234682-A-G is described in ClinVar as [Benign]. Clinvar id is 1236912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBD	ENST00000429817.1	c.-97-152T>C		intron_variant		5
HBD	ENST00000643122.1	c.-28-221T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64068 AN: 151876 Hom.: 14986 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.490 AC: 187472 AN: 382646 Hom.: 47739 Cov.: 0 AF XY: 0.495 AC XY: 100918 AN XY: 203960

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.728

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.422 AC: 64106 AN: 151994 Hom.: 14996 Cov.: 32 AF XY: 0.430 AC XY: 31943 AN XY: 74276

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.482

Alfa AF: 0.449 Hom.: 7051

Bravo AF: 0.423

Asia WGS AF: 0.596 AC: 2073 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.70
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3813727; hg19: chr11-5255912;