11-5242623-A-G

Position:

• chr11-5242623-A-G

Variant summary

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

The NR_001589.1(HBBP1):​n.367-376T>C 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 0.0302 in 152,258 control chromosomes in the GnomAD database, including 186 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 0.030 (186 hom., cov: 32)
• Consequence: HBBP1 NR_001589.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBBP1	NR_001589.1	n.367-376T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBBP1	ENST00000433329.1	n.312-376T>C		intron_variant, non_coding_transcript_variant
	ENST00000454892.2	n.308-376T>C		intron_variant, non_coding_transcript_variant		2
HBD	ENST00000643122.1	c.-29+827T>C		intron_variant				ENSP00000494708	P1

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4556 AN: 152140 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0302 AC: 4601 AN: 152258 Hom.: 186 Cov.: 32 AF XY: 0.0314 AC XY: 2341 AN XY: 74460

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0647

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0126 Hom.: 21

Bravo AF: 0.0386

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16912210; hg19: chr11-5263853;