11-5242916-T-G

Variant names:

• chr11-5242916-T-G
• rs2071348
• ENST00000643122.1:c.-29+534A>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+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
• Publications: 39 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=-0.82).
• 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 rank	MANE	Protein	UniProt
HBBP1	NR_001589.1	n.366+190A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000643122.1	c.-29+534A>C		intron_variant	Intron 1 of 3			ENSP00000494708.1
HBBP1	ENST00000433329.1	n.311+190A>C		intron_variant	Intron 2 of 2	6
ENSG00000290652	ENST00000454892.2	n.307+190A>C		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.163 AC: 6765 AN: 41514

American (AMR) AF: 0.215 AC: 3290 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3464

East Asian (EAS) AF: 0.118 AC: 612 AN: 5168

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4816

European-Finnish (FIN) AF: 0.223 AC: 2356 AN: 10582

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22241 AN: 67960

Other (OTH) AF: 0.259 AC: 547 AN: 2108

Alfa AF: 0.301 Hom.: 24764

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
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs2071348; hg19: chr11-5264146;