rs9399137

Positions:

• chr6-135097880-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000529882.5(HBS1L):​c.88+5048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,414 control chromosomes in the GnomAD database, including 3,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.20 (3659 hom., cov: 32)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-135097880-T-C is Benign according to our data. Variant chr6-135097880-T-C is described in Lovd as [Likely_benign].
• 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000529882.5	c.88+5048A>G		intron_variant		4		ENSP00000433030

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29748 AN: 151300 Hom.: 3657 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.197 AC: 29754 AN: 151414 Hom.: 3659 Cov.: 32 AF XY: 0.197 AC XY: 14548 AN XY: 74014

Gnomad4 AFR AF: 0.0680

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.163

Alfa AF: 0.231 Hom.: 3886

Bravo AF: 0.179

Asia WGS AF: 0.151 AC: 522 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9399137; hg19: chr6-135419018;