ENST00000643122.1:c.-29+827T>C

Variant names:

• chr11-5242623-A-G
• rs16912210
• ENST00000643122.1:c.-29+827T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643122.1(HBD):​c.-29+827T>C variant causes a intron 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: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 8 publications found

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:4828): (hemoglobin subunit beta pseudogene 1)

ENSG00000290652 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643122.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBBP1	NR_001589.1		n.367-376T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBD	ENST00000643122.1		c.-29+827T>C		intron	N/A	ENSP00000494708.1
	HBBP1	ENST00000433329.1	TSL:6	n.312-376T>C		intron	N/A
	ENSG00000290652	ENST00000454892.2	TSL:2	n.308-376T>C		intron	N/A

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

African (AFR) AF: 0.0743 AC: 3083 AN: 41514

American (AMR) AF: 0.0581 AC: 889 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.0647 AC: 335 AN: 5178

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4828

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00135 AC: 92 AN: 68030

Other (OTH) AF: 0.0336 AC: 71 AN: 2112

Alfa AF: 0.0182 Hom.: 104

Bravo AF: 0.0386

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16912210; hg19: chr11-5263853;