11-5242916-T-G

Position:

• chr11-5242916-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643122.1(HBD):​c.-29+534A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,114 control chromosomes in the GnomAD database, including 5,308 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5308 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

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]

HBBP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBBP1	NR_001589.1	n.366+190A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000643122.1	c.-29+534A>C		intron_variant				ENSP00000494708.1
HBBP1	ENST00000433329.1	n.311+190A>C		intron_variant		6
ENSG00000290652	ENST00000454892.2	n.307+190A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38157 AN: 152000 Hom.: 5310 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38161 AN: 152114 Hom.: 5308 Cov.: 32 AF XY: 0.246 AC XY: 18256 AN XY: 74362

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.259

Alfa AF: 0.307 Hom.: 11093

Bravo AF: 0.243

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.90
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071348; hg19: chr11-5264146;