rs66650371

Positions:

• chr6-135097494-TTAC-T
• chr6-135097494-TTAC-TTACTAC

Variant summary

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

The ENST00000529882.5(HBS1L):​c.88+5431_88+5433delGTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,074 control chromosomes in the GnomAD database, including 3,618 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3618 hom., cov: 26)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

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]

(HGNC:):

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	Protein	UniProt
		n.135097495_135097497delTAC		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000529882.5	c.88+5431_88+5433delGTA		intron_variant		4		ENSP00000433030.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29683 AN: 151956 Hom.: 3616 Cov.: 26

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.195 AC: 29689 AN: 152074 Hom.: 3618 Cov.: 26 AF XY: 0.195 AC XY: 14487 AN XY: 74318

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.161

Alfa AF: 0.229 Hom.: 569

Bravo AF: 0.178

Asia WGS AF: 0.150 AC: 522 AN: 3478

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: rs66650371; hg19: chr6-135418632;