chr6-135097899-AC-A

Position:

• chr6-135097899-AC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000529882.5(HBS1L):​c.88+5028del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,964 control chromosomes in the GnomAD database, including 4,542 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4542 hom., cov: 25)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

Genes affected

HBS1L (HGNC:4834): (HBS1 like translational GTPase) This gene encodes a member of the GTP-binding elongation factor family. It is expressed in multiple tissues with the highest expression in heart and skeletal muscle. The intergenic region of this gene and the MYB gene has been identified to be a quantitative trait locus (QTL) controlling fetal hemoglobin level, and this region influnces erythrocyte, platelet, and monocyte counts as well as erythrocyte volume and hemoglobin content. DNA polymorphisms at this region associate with fetal hemoglobin levels and pain crises in sickle cell disease. A single nucleotide polymorphism in exon 1 of this gene is significantly associated with severity in beta-thalassemia/Hemoglobin E. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBS1L	ENST00000529882.5	c.88+5028del		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36239 AN: 151846 Hom.: 4537 Cov.: 25

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.239 AC: 36261 AN: 151964 Hom.: 4542 Cov.: 25 AF XY: 0.237 AC XY: 17599 AN XY: 74250

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.199

Alfa AF: 0.255 Hom.: 635

Bravo AF: 0.229

Asia WGS AF: 0.179 AC: 619 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34778774; hg19: chr6-135419037;