rs10128556

chr11-5242453-C-T

Variant summary

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

The NR_001589.1(HBBP1):n.367-206G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,988 control chromosomes in the GnomAD database, including 5,127 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 (5127 hom., cov: 31)
• Consequence: HBBP1 NR_001589.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

Genes affected

HBBP1 (HGNC:4828): (hemoglobin subunit beta pseudogene 1)

(HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBBP1	NR_001589.1	n.367-206G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBBP1	ENST00000433329.1	n.312-206G>A		intron_variant, non_coding_transcript_variant
	ENST00000454892.2	n.308-206G>A		intron_variant, non_coding_transcript_variant		2
HBD	ENST00000643122.1	c.-29+997G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37530 AN: 151870 Hom.: 5128 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.247 AC: 37538 AN: 151988 Hom.: 5127 Cov.: 31 AF XY: 0.242 AC XY: 17995 AN XY: 74314

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.258

Alfa AF: 0.285 Hom.: 843

Bravo AF: 0.239

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.79
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10128556; hg19: chr11-5263683;