rs34975911

chr11-5234560-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5 BP4

The ENST00000643122.1(HBD):c.-28-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 748,812 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -1.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PP5: Variant 11-5234560-A-G is Pathogenic according to our data. Variant chr11-5234560-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 15072.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).. Strength limited to SUPPORTING due to the PP5.

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.-97-30T>C		intron_variant		5
HBD	ENST00000643122.1	c.-28-99T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000280 AC: 167 AN: 596524 Hom.: 2 Cov.: 6 AF XY: 0.000245 AC XY: 79 AN XY: 322550

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00468

Gnomad4 SAS exome AF: 0.000108

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000290

Gnomad4 OTH exome AF: 0.0000314

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74466

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000756

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

delta Thalassemia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 1992

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	1.5
Dann	Benign	0.67

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: rs34975911; hg19: chr11-5255790;